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... if these drugs are used in acute pain, there will be no analgesic effect). These drugs, on the contrary, have analgesic effects in chronic pain due to their modulatory effects on the nervous system activity. Psychological Interventions If modulation of the CNS can relieve chronic pain, then one can argue that other forms of CNS modulation can also result in pain amelioration. Indeed, there are a number of studies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral ...

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...S), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pa...

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...idate tool to modulate brain activity is repetitive transcranial magnetic stimulation (rTMS). TMS is a form of brain stimulation that is based on a time-varying magnetic field. A small coil with a powerful and rapidly alternating electrical current is applied over the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable beha...

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...er the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et a...

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...herapy focusing on the modulation of this cortical dysfunctional activity would be desirable. The data suggest that rTMS is a treatment that can modulate cortical excitability in a painless and noninvasive way and can be effective in the relief of chronic pain in patients with chronic pancreatitis. If rTMS can be effective to relieve CAVP, other neuromodulatory approaches might also result in the same therapeutic effect. For instance, invasive brain stimulation, such as deep brain or epidural cortical stimulation, can be successfully used to treat neuropsychiatric disorders, such as depression[137], epilepsy[138], and, indeed, somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique fo...

Citation Context

... if these drugs are used in acute pain, there will be no analgesic effect). These drugs, on the contrary, have analgesic effects in chronic pain due to their modulatory effects on the nervous system activity. Psychological Interventions If modulation of the CNS can relieve chronic pain, then one can argue that other forms of CNS modulation can also result in pain amelioration. Indeed, there are a number of studies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral ...

Citation Context

...n electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp....

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...S), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pa...

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...ents report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychological treatment in IBS[100]. In the intention-to-treat and per-protocol analyses, CBT shows a significant beneficial response in 70% of the patients vs. 37% of the patients receiving education. The least beneficial effect is observed for IBS patients with depression. A further study compared paroxetine with psychotherapy and routine care in patients with severe IBS, evaluating also the economical impact of such therapies. The results showed that CBT improves health-r...

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...ulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[141] and epilepsy[142]. Furthermore, in a preliminary study, we showed that this technique is associated with a significant analgesic effect in patients with central pain due to spinal cord injury[143]. This device has the advantage of being simpler and cheaper than rTMS and perhaps can be designed as a portable device in the future. Other targets in the CNS, rather than cortical areas, may be important in pain relief in CAVP. For instance, a recent study has shown that spinal cord stimulation (SCS) is an efficacious technique for the treatment of visceral pain syndromes. In this study, there was a substantial overall mean reduction in the Visual Analog Scale (VAS) pain scores as well as a decrease in narcotic use with minimal complications. Spinal cord stimulation might be an effective, re...

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...S often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less...

Citation Context

...S often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less...

Citation Context

...somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[141] and epilepsy[142]. Furthermore, in a preliminary study, we showed that this technique is associated with a significant analgesic effect in patients with central pain due to spinal cord injury[143]. This device has the advantage of being simpler and cheaper than rTMS and perhaps can be designed as a portable device in the future. Other targets in the CNS, rather than cortical areas, may be important in pain relief in CAVP. For instance, a recent study has shown that spinal cord stimulation (SCS) is an efficacious technique for the treatment of visceral pain syndromes. In this study, there was a substantial over...

Citation Context

...S), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pa...

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...m. CBT vs. educational therapy was examined in one of the largest studies of psychological treatment in IBS[100]. In the intention-to-treat and per-protocol analyses, CBT shows a significant beneficial response in 70% of the patients vs. 37% of the patients receiving education. The least beneficial effect is observed for IBS patients with depression. A further study compared paroxetine with psychotherapy and routine care in patients with severe IBS, evaluating also the economical impact of such therapies. The results showed that CBT improves health-related quality of life at no additional cost[101]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 482 Further studies are needed to clarify which patients are more likely to respond to psychological treatments and to elucidate the underlying mechanisms for the beneficial effects of these interventions. Nonpharmacological Approaches Patients who fail medical treatments often are referred for nerve blocks or potential surgical resections. However, percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis. Even among respon...

Citation Context

...n electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp....

Citation Context

...38], and, indeed, somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[141] and epilepsy[142]. Furthermore, in a preliminary study, we showed that this technique is associated with a significant analgesic effect in patients with central pain due to spinal cord injury[143]. This device has the advantage of being simpler and cheaper than rTMS and perhaps can be designed as a portable device in the future. Other targets in the CNS, rather than cortical areas, may be important in pain relief in CAVP. For instance, a recent study has shown that spinal cord stimulation (SCS) is an efficacious technique for the treatment of visceral pain syndromes. In this study, there was ...

Citation Context

...ychological treatments and to elucidate the underlying mechanisms for the beneficial effects of these interventions. Nonpharmacological Approaches Patients who fail medical treatments often are referred for nerve blocks or potential surgical resections. However, percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis. Even among responders, symptoms frequently recur within 2–6 months, albeit the nerve block can be repeated as needed. Furthermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all othe...

Citation Context

...L (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pain syndromes[130,135]. In addition, Lefaucher et al. studied 60 patients suffering from intractable pain. These patients underwent one session of active or sham rTMS in random order. The authors showed that pain reduction was signif...

Citation Context

...ychological treatments and to elucidate the underlying mechanisms for the beneficial effects of these interventions. Nonpharmacological Approaches Patients who fail medical treatments often are referred for nerve blocks or potential surgical resections. However, percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis. Even among responders, symptoms frequently recur within 2–6 months, albeit the nerve block can be repeated as needed. Furthermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all othe...

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...d understood compared to that of TCAs and it has been proposed that it may be associated with its primary effect on depression or because of an increase in the serotonin levels. Other drugs that are commonly used along with antidepressants are the anticonvulsants (such as phenitoin, carbamazepine, valproic acid, clonazepam, and newer agents, gabapentin and lamotrigine). These drugs may be particularly beneficial for chronic pain. The mechanism of action of anticonvulsants in chronic pain is unclear, but their effects on reducing the excitability of the nervous system may play an important role[89,90,91]. Although some benzodiazepines used as antiepileptic drugs are commonly employed in patients with pain, the prolonged use of this drug does not offer benefits for these patients and can lead to the phenomenon of tolerance and dependence. It is interesting to note that antidepressants and anticonvulsants are not associated with a primary analgesic effect (i.e., if these drugs are used in acute pain, there will be no analgesic effect). These drugs, on the contrary, have analgesic effects in chronic pain due to their modulatory effects on the nervous system activity. Psychological Interventions ...

Citation Context

...ional activity would be desirable. The data suggest that rTMS is a treatment that can modulate cortical excitability in a painless and noninvasive way and can be effective in the relief of chronic pain in patients with chronic pancreatitis. If rTMS can be effective to relieve CAVP, other neuromodulatory approaches might also result in the same therapeutic effect. For instance, invasive brain stimulation, such as deep brain or epidural cortical stimulation, can be successfully used to treat neuropsychiatric disorders, such as depression[137], epilepsy[138], and, indeed, somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[141] and epilepsy[142]. Furthermore, in a prelimin...

Citation Context

...S often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less...

Citation Context

...can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is...

Citation Context

...11,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural st...

Citation Context

...Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pa...

Citation Context

...udies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychologic...

Citation Context

...se pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychological treatment in IBS[100]. In the intention-to-treat and per-protocol analyses, CBT shows a significant beneficial response in 70% of the patients vs. 37% of the pati...

Citation Context

...Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pa...

Citation Context

...er the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et a...

Citation Context

...S often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less...

Citation Context

...Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pa...

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...on the nervous system activity. Psychological Interventions If modulation of the CNS can relieve chronic pain, then one can argue that other forms of CNS modulation can also result in pain amelioration. Indeed, there are a number of studies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbi...

Citation Context

...er the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et a...

Citation Context

...er the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et a...

Citation Context

...L (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pain syndromes[130,135]. In addition, Lefaucher et al. studied 60 patients suffering from intractable pain. These patients underwent one session of active or sham rTMS in random order. The authors showed that pain reduction was signif...

Citation Context

...ffective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychological treatment in IBS[100]. In the intention-to-treat and per-protocol analyses, CBT shows a significant beneficial response in 70% of the patients vs. 37% of the patients receiving education. The least beneficial effect is observed for IBS patients with depression. A further study compared paroxetine with psychotherapy and routine care in patients with severe IBS, evaluating also the economical impact of such therapies. The results showed that CBT improves health-related quality of life at no additional cost[101]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 482 Furthe...

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...S), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pa...

Citation Context

...d understood compared to that of TCAs and it has been proposed that it may be associated with its primary effect on depression or because of an increase in the serotonin levels. Other drugs that are commonly used along with antidepressants are the anticonvulsants (such as phenitoin, carbamazepine, valproic acid, clonazepam, and newer agents, gabapentin and lamotrigine). These drugs may be particularly beneficial for chronic pain. The mechanism of action of anticonvulsants in chronic pain is unclear, but their effects on reducing the excitability of the nervous system may play an important role[89,90,91]. Although some benzodiazepines used as antiepileptic drugs are commonly employed in patients with pain, the prolonged use of this drug does not offer benefits for these patients and can lead to the phenomenon of tolerance and dependence. It is interesting to note that antidepressants and anticonvulsants are not associated with a primary analgesic effect (i.e., if these drugs are used in acute pain, there will be no analgesic effect). These drugs, on the contrary, have analgesic effects in chronic pain due to their modulatory effects on the nervous system activity. Psychological Interventions ...

Citation Context

...udies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychologic...

Citation Context

...ychological treatments and to elucidate the underlying mechanisms for the beneficial effects of these interventions. Nonpharmacological Approaches Patients who fail medical treatments often are referred for nerve blocks or potential surgical resections. However, percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis. Even among responders, symptoms frequently recur within 2–6 months, albeit the nerve block can be repeated as needed. Furthermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all othe...

Citation Context

...hermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all other pain relief treatments. The procedure can be debilitating, leading to exocrine and endocrine dysfunction. Interestingly, even with the complete removal of the gland, pancreatic pain persists in up to 30% of patients[49,109], suggesting secondary dysfunction of the CNS. Despite the fact that surgical procedures can provide some benefit for patients with chronic visceral pain, they are associated with adverse effects and frequent treatment failure. The main reason for lack of efficacy is the fact that chronic ...

Citation Context

...udies directly evaluating the effect of psychological interventions on gastrointestinal visceral sensitivity since it has been shown that psychological distress can decrease pain threshold[41,92,93]. A recent meta-analysis of psychological treatments found an overall benefit in reducing pain and other symptoms, such as anxiety and depression, in patients with IBS[94]. Some psychological interventions are related to forms of hypnotherapy. Controlled studies with IBS patients report improvements in abnormal sensory perception with hypnotherapy compared to no treatment or supportive psychotherapy[95,96,97]. Hypnotherapy is effective on both short- and long-term symptom scores in functional dyspepsia as well, with a reduction in medication use and consultation rate[98]. Cognitive behavioral therapy (CBT) has also been investigated for adjuvant treatment of chronic pain. It has been shown that visceral pain is associated with an increased activity in the limbic system and a recent study showed that CBT is associated with changes in the activity of cingulate gyrus[99], an important component of the limbic system. CBT vs. educational therapy was examined in one of the largest studies of psychologic...

Citation Context

...hermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all other pain relief treatments. The procedure can be debilitating, leading to exocrine and endocrine dysfunction. Interestingly, even with the complete removal of the gland, pancreatic pain persists in up to 30% of patients[49,109], suggesting secondary dysfunction of the CNS. Despite the fact that surgical procedures can provide some benefit for patients with chronic visceral pain, they are associated with adverse effects and frequent treatment failure. The main reason for lack of efficacy is the fact that chronic ...

Citation Context

...hermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all other pain relief treatments. The procedure can be debilitating, leading to exocrine and endocrine dysfunction. Interestingly, even with the complete removal of the gland, pancreatic pain persists in up to 30% of patients[49,109], suggesting secondary dysfunction of the CNS. Despite the fact that surgical procedures can provide some benefit for patients with chronic visceral pain, they are associated with adverse effects and frequent treatment failure. The main reason for lack of efficacy is the fact that chronic ...

Citation Context

...S often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et al.: Novel treatments for visceral pain TheScientificWorldJOURNAL (2006) 6, 472–490 483 FIGURE 4. Picture showing the application of rTMS treatment; the rTMS coil is held over the subject’s scalp. Clinically, several studies have shown that the cortical activity modulation by rTMS can be successfully used in the treatment of various neuropsychiatric disorders[124,125,126,127,128], as well as the treatment of chronic pain[129,130,131,132]. The notion that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less...

Citation Context

... that brain modulation may be an effective therapy for chronic pain syndromes is based on the fact that chronic electrical epidural stimulation of the precentral cortex can improve drug-resistant neurogenic pain[133,134]. Presumably this is due to inhibition of nociceptive neurons at cortical levels through non-noxious fibers from the motor cortex. However, this technique is invasive and requires a craniotomy. Two recently published studies using rTMS applied to the motor cortex reported that this treatment resulted in less pain in patients with therapy-resistant chronic somatic pain syndromes[130,135]. In addition, Lefaucher et al. studied 60 patients suffering from intractable pain. These patients underwent one session of active or sham rTMS in random order. The authors showed that pain reduction was significantly greater following real than sham rTMS[129]. Because of these promissory results of brain stimulation for the treatment of chronic pain, a recent study has investigated whether rTMS is effective in the relief of chronic visceral pain in patients with chronic pancreatitis[136]. The effect of low- and high-frequency rTMS was studied. Five participants with idiopathic chronic pancre...

Citation Context

...TMS can be effective to relieve CAVP, other neuromodulatory approaches might also result in the same therapeutic effect. For instance, invasive brain stimulation, such as deep brain or epidural cortical stimulation, can be successfully used to treat neuropsychiatric disorders, such as depression[137], epilepsy[138], and, indeed, somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[141] and epilepsy[142]. Furthermore, in a preliminary study, we showed that this technique is associated with a significant analgesic effect in patients with central pain due to spinal cord injury[143]. This device has the advantage of being simpler and cheaper than rTMS and perhaps can be ...

Citation Context

...d understood compared to that of TCAs and it has been proposed that it may be associated with its primary effect on depression or because of an increase in the serotonin levels. Other drugs that are commonly used along with antidepressants are the anticonvulsants (such as phenitoin, carbamazepine, valproic acid, clonazepam, and newer agents, gabapentin and lamotrigine). These drugs may be particularly beneficial for chronic pain. The mechanism of action of anticonvulsants in chronic pain is unclear, but their effects on reducing the excitability of the nervous system may play an important role[89,90,91]. Although some benzodiazepines used as antiepileptic drugs are commonly employed in patients with pain, the prolonged use of this drug does not offer benefits for these patients and can lead to the phenomenon of tolerance and dependence. It is interesting to note that antidepressants and anticonvulsants are not associated with a primary analgesic effect (i.e., if these drugs are used in acute pain, there will be no analgesic effect). These drugs, on the contrary, have analgesic effects in chronic pain due to their modulatory effects on the nervous system activity. Psychological Interventions ...

Citation Context

...ychological treatments and to elucidate the underlying mechanisms for the beneficial effects of these interventions. Nonpharmacological Approaches Patients who fail medical treatments often are referred for nerve blocks or potential surgical resections. However, percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis. Even among responders, symptoms frequently recur within 2–6 months, albeit the nerve block can be repeated as needed. Furthermore, serious complications have been described associated with this procedure[102,103,104,105]. Surgery is indicated in selected individuals and involves resection usually of a portion of the involved organ. For instance, in chronic pancreatitis, the removal of the pancreas (typically the tail or head) and less commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all othe...

Citation Context

...s commonly the entire pancreas has been advocated as a procedure to reduce pain in these patients. Although resection of the pancreas may provide pain relief in up to 60% of selected patients with chronic pancreatitis, including those with disease extending to the tail of the pancreas[106,107,108], total pancreatectomy should be reserved as a last resort in those who fail all other pain relief treatments. The procedure can be debilitating, leading to exocrine and endocrine dysfunction. Interestingly, even with the complete removal of the gland, pancreatic pain persists in up to 30% of patients[49,109], suggesting secondary dysfunction of the CNS. Despite the fact that surgical procedures can provide some benefit for patients with chronic visceral pain, they are associated with adverse effects and frequent treatment failure. The main reason for lack of efficacy is the fact that chronic visceral pain syndromes may result in CNS changes that cannot be reverted by a change in the peripheral afferent system. Therefore, new approaches should target brain cortical areas, rather than the PNS, to relieve pain in patients with chronic visceral pain. Possible Future Therapeutic Approaches: Brain Stim...

Citation Context

...er the brain cortex (Fig. 4). The continuous change in the electrical current that flows through the coil can generate a time-varying magnetic field that passes unimpeded through skin and bones, generating an electric current inside the skull, where it can be focused and restricted to small areas depending on the coil geometry and shape[110]. It has been demonstrated that this current, if applied repetitively (rTMS), might induce a cortical modulation that lasts beyond the time of stimulation. Several animal and human studies establish that rTMS can modulate brain cortex activity noninvasively[110,111,112,113,114,115]. The modulation may range from suppression to facilitation of activity in the targeted cortical area, depending on the stimulation parameters (particularly frequency of stimulation)[114,116,117]. While low-frequency (1 Hz) rTMS can decrease the excitability of targeted cortical regions resulting in a measurable behavioral changes, high-frequency (20 Hz) rTMS often has the opposite effects[114,115,117,118,119,120,121]. Furthermore, several animal studies report that rTMS is associated with modulation of NMDA binding sites[122] and can increase immediate-early gene expression[123]. Patrizi et a...

Citation Context

...this treatment resulted in less pain in patients with therapy-resistant chronic somatic pain syndromes[130,135]. In addition, Lefaucher et al. studied 60 patients suffering from intractable pain. These patients underwent one session of active or sham rTMS in random order. The authors showed that pain reduction was significantly greater following real than sham rTMS[129]. Because of these promissory results of brain stimulation for the treatment of chronic pain, a recent study has investigated whether rTMS is effective in the relief of chronic visceral pain in patients with chronic pancreatitis[136]. The effect of low- and high-frequency rTMS was studied. Five participants with idiopathic chronic pancreatitis underwent (in random order) six sessions of rTMS of either the right and left SII with different parameters of stimulation: right 1 Hz-rTMS (R-1Hz), left 1 Hz-rTMS (L-1Hz), right sham (R-sham), left sham (L-sham), right 20 Hz-rTMS (R-20Hz), and left 20 Hz rTMS (L-20Hz). Each participant had chronic daily pain for at least 3 years. Baseline pain scores on a visual analogue scale were obtained during the 2 weeks prior to treatment. Pain levels were assessed daily throughout the TMS se...

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... on the modulation of this cortical dysfunctional activity would be desirable. The data suggest that rTMS is a treatment that can modulate cortical excitability in a painless and noninvasive way and can be effective in the relief of chronic pain in patients with chronic pancreatitis. If rTMS can be effective to relieve CAVP, other neuromodulatory approaches might also result in the same therapeutic effect. For instance, invasive brain stimulation, such as deep brain or epidural cortical stimulation, can be successfully used to treat neuropsychiatric disorders, such as depression[137], epilepsy[138], and, indeed, somatic and central pain[134,139]. Therefore, similar to rTMS, it could have a positive impact on visceral pain as well. Moreover, a further, less-invasive technique of brain stimulation — vagus nerve stimulation (VNS) — has been reported to have antidepressant effects[140] and perhaps might have some analgesic effects in patients with CAVP. Finally, another type of noninvasive brain stimulation — transcranial direct current stimulation — is being explored as a treatment for epilepsy and depression. Preliminary data have shown positive results of this technique for depression[14...