The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel a 2 -d ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.Mayo Clin Proc. 2010;85(3)(suppl):S3-S14 DPN = diabetic peripheral neuropathy; HIV = human immunodeficiency virus; HRQoL = health-related quality of life; NeuPSIG = Neuropathic Pain Special Interest Group; NP = neuropathic pain; PHN = postherpetic neuralgia; RCT = randomized clinical trial; SSNRI = selective serotonin norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant

Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala--the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.

a short style of TCC was found to be an effective way to improve many fitness measures in elderly women over a 3-month period. TCC was also found to be significantly better than brisk walking in enhancing certain measures of fitness including lower extremity strength, balance and flexibility.

à These authors contributed equally to this work.Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist. Acupuncture is a minimally-invasive and conservative therapeutic option, and while rooted in a complex practice ritual, acupuncture overlaps significantly with many conventional peripherally-focused neuromodulatory therapies. However, the neurophysiological mechanisms by which acupuncture impacts accepted subjective/psychological and objective/physiological outcomes are not well understood. Eligible patients (n = 80, 65 female, age: 49.3 AE 8.6 years) were enrolled and randomized into three intervention arms: (i) verum electro-acupuncture 'local' to the more affected hand; (ii) verum electro-acupuncture at 'distal' body sites, near the ankle contralesional to the more affected hand; and (iii) local sham electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome Questionnaire assessed pain and paraesthesia symptoms at baseline, following therapy and at 3-month follow-up. Nerve conduction studies assessing median nerve sensory latency and brain imaging data were acquired at baseline and following therapy. Functional magnetic resonance imaging assessed somatotopy in the primary somatosensory cortex using vibrotactile stimulation over three digits (2, 3 and 5). While all three acupuncture interventions reduced symptom severity, verum (local and distal) acupuncture was superior to sham in producing improvements in neurophysiological outcomes, both local to the wrist (i.e. median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 cortical separation distance). Moreover, greater improvement in second/third interdigit cortical separation distance following verum acupuncture predicted sustained improvements in symptom severity at 3-month follow-up. We further explored potential differential mechanisms of local versus distal acupuncture using diffusion tensor imaging of white matter microstructure adjacent to the primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 49.7 AE 9.9 years old), patients with carpal tunnel syndrome demonstrated increased fractional anisotropy in several regions and, for these regions we found that improvement in median nerve latency was associated with reduction of fractional anisotropy near (i) contralesional hand area following verum, but not sham, acupuncture; (ii) ipsilesional hand area following local, but not distal or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not local or sham, acupuncture. As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex ...

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[3][4][5] In some studies, investigators reported that more than 40% of patients with implanted devices for pain control experience adverse events 6 ; up to 67.7% of patients treated with lumbar surgery for back pain reported that their pain was worse after surgery, 7 and at least moderate adverse effects have been reported to occur in 30% to 61% of all patients who undergo spinal manipulations. 8 These findings do not argue against the use of such treatments but serve as reminders of limitations and possible harmful effects. The mean duration of pain in patients who seek treatment at chronic pain treatment facilities is approximately 7 years. 9 Consequently, all domains of their lives may have been compromised for a substantial amount of time. It is hardly surprising that levels of emotional distress for patients with persistent pain are high. Estimates suggest that at least 1 current psychiatric diagnosis is present in 59% of patients with chronic back pain treated at pain facilities and at least 1 lifetime psychiatric diagnosis is present in 77% of these patients. 10 In contrast, community estimates are 15% for at least 1 current psychiatric diagnosis and 29% to 38% Chronic neuropathic pain is a prevalent problem that eludes cure and adequate treatment. The persistence of intense and aversive symptoms, inadequacy of available treatments, and impact of such pain on all aspects of functioning underscore the important role of several psychosocial factors in causing, maintaining, and amplifying the perception of pain severity, coping adequacy, adaptation, impaired physical function, and emotional distress responses. Moreover, these factors have an influential role in response to treatment recommendations. In this article, we (1) review the prevalence and nature of emotional distress, (2) describe and propose methods for screening and comprehensive psychosocial assessment, and (3) review evidence supporting the potential complementary role of psychosocial treatments of patients with chronic pain. The cognitive-behavioral perspective and treatment approach are emphasized because the greatest amount of evidence supports their benefits. Published results of psychological treatments are modest; however, the same indictment can be placed on currently available pharmacological, medical, and interventional treatments for patients with chronic pain. We note the limited research on the effectiveness of psychological treatment specifically applied to patients with chronic neuropathic pain but suggest that it is reasonable to extrapolate from successful trials in other types of chronic pain. Furthermore, psychological approaches should not be viewed as alternatives but rather should be integrated as part of a comprehensive approach to the treatment of patients with chronic neuropathic pain. Mayo Clin © 2010 Mayo Foundation for Medical Education and ResearchC hronic neuropathic pain is a prevalent problem that eludes successful treatment. Despite increasing knowledge of the neurophysiologic factors underlying neuropathic pa...

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first through fourth digits. We hypothesize that aberrant afferent input from CTS will lead to maladaptive cortical plasticity, which may be corrected by appropriate therapy. Functional MRI (fMRI) scanning and clinical testing was performed on CTS patients at baseline and after 5 weeks of acupuncture treatment. As a control, healthy adults were also tested 5 weeks apart. During fMRI, sensory stimulation was performed for median nerve innervated digit 2 (D2) and digit 3 (D3), and ulnar nerve innervated digit 5 (D5). Surface-based and region of interest (ROI)-based analyses demonstrated that while the extent of fMRI activity in contralateral Brodmann Area 1 (BA 1) and BA 4 was increased in CTS compared to healthy adults, after acupuncture there was a significant decrease in contralateral BA 1 (P < 0.005) and BA 4 (P < 0.05) activity during D3 sensory stimulation. Healthy adults demonstrated no significant test-retest differences for any digit tested. While D3/D2 separation was contracted or blurred in CTS patients compared to healthy adults, the D2 SI representation shifted laterally after acupuncture treatment, leading to increased D3/D2 separation. Increasing D3/D2 separation correlated with decreasing paresthesias in CTS patients (P < 0.05). As CTS-induced paresthesias constitute diffuse, synchronized, multidigit symptomatology, our results for maladaptive change and correction are consistent with Hebbian plasticity mechanisms. Acupuncture, a somatosensory conditioning stimulus, shows promise in inducing beneficial cortical plasticity manifested by more focused digital representations.

The linkage between brain response to acupuncture and subsequent analgesia remains poorly understood. Our aim was to evaluate this linkage in chronic pain patients with carpal tunnel syndrome (CTS). Brain response to electroacupuncture (EA) was evaluated with functional MRI. Subjects were randomized to 3 groups: (1) EA applied at local acupoints on the affected wrist (PC-7 to TW-5), (2) EA at distal acupoints (contralateral ankle, SP-6 to LV-4), and (3) sham EA at nonacupoint locations on the affected wrist. Symptom ratings were evaluated prior to and following the scan. Subjects in the local and distal groups reported reduced pain. Verum EA produced greater reduction of paresthesia compared to sham. Compared to sham EA, local EA produced greater activation in insula and S2 and greater deactivation in ipsilateral S1, while distal EA produced greater activation in S2 and deactivation in posterior cingulate cortex. Brain response to distal EA in prefrontal cortex (PFC) and brain response to verum EA in S1, SMA, and PFC were correlated with pain reduction following stimulation. Thus, while greater activation to verum acupuncture in these regions may predict subsequent analgesia, PFC activation may specifically mediate reduced pain when stimulating distal acupoints.