The journal of pain : official journal of the American Pain Society
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Injury- or disease-induced artemin (ARTN) signaling can sensitize primary afferents and contribute to persistent pain. We demonstrate that administration of an ARTN neutralizing antibody, anti-artemin (α-ARTN), can block the development of, and reverse already established, bladder hyperalgesia associated with cyclophosphamide-induced cystitis in mice. We further demonstrate that α-ARTN therapy blocks upregulation of TRPA1, an ion channel contributing to persistent bladder pain during cyclophosphamide-induced cystitis, and decreases phospho-ERK1/2 immunoreactivity in regions of the spinal cord receiving bladder afferent input. Thus, α-ARTN is a promising novel therapeutic approach for treatment of bladder hyperalgesia that may be associated with interstitial cystitis/painful bladder syndrome, as well as cystitis associated with antitumor or immunosuppressive cyclophosphamide therapy. ⋯ α-ARTN therapy effectively prevented and reversed ongoing bladder hyperalgesia in an animal model of cystitis, indicating its potential as an efficacious treatment strategy for ongoing bladder pain associated with interstitial cystitis/painful bladder syndrome.
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The study explored the analgesic effects of transcranial direct current stimulation (tDCS) over the motor cortex on postamputation phantom limb pain (PLP). Eight subjects with unilateral lower or upper limb amputation and chronic PLP were enrolled in a crossover, double-blind, sham-controlled treatment program. For 5 consecutive days, anodal (active or sham) tDCS was applied over the motor cortex for 15 minutes at an intensity of 1.5 mA. The 5-day treatment with active, but not sham, tDCS induced a sustained decrease in background PLP and in the frequency of PLP paroxysms, which lasted for 1 week after the end of treatment. Moreover, on each day of active tDCS, patients reported an immediate PLP relief, along with an increased ability to move their phantom limb. Patients' immediate responses to sham tDCS, on the contrary, were variable, marked by an increase or decrease of PLP levels from baseline. These results show that a 5-day treatment of motor cortex stimulation with tDCS can induce stable relief from PLP in amputees. Neuromodulation targeting the motor cortex appears to be a promising option for the management of this debilitating neuropathic pain condition, which is often refractory to classic pharmacologic and surgical treatments. ⋯ The study describes sustained and immediate effects of motor cortex stimulation by tDCS on postamputation PLP, whose analgesic action seems linked to the motor reactivation of the phantom limb. These results are helpful for the exploitation of tDCS as a therapeutic tool for the management of neuropathic pain.
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Although nonnoxious, high-frequency electrical stimulation applied segmentally (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been proposed to modulate pain, the mechanisms underlying analgesia remain poorly understood. To further elucidate how TENS modulates pain, we examined evoked responses to noxious thermal stimuli after the induction of sensitization using capsaicin in healthy volunteers. We hypothesized that sensitization caused by capsaicin application would unmask TENS analgesia, which could not be detected in the absence of sensitization. Forty-nine healthy subjects took part in a series of experiments. The experiments comprised the application of topical capsaicin (.075%) on the left hand in the C6 dermatome, varying the location of TENS (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing rating of perception (numeric rating scale: 0-10) and evoked potentials to noxious contact heat stimuli. The extrasegmental site was included as a control condition because previous studies indicate no analgesic effect to remote conventional TENS. Conventional TENS had no significant effect on rating or sensory evoked potentials in subjects untreated with capsaicin. However, segmental TENS applied in conjunction with capsaicin significantly reduced sensation to noxious thermal stimuli following a 60-minute period of sensitization. ⋯ The study indicates that sensitization with capsaicin unmasks the analgesic effect of conventional TENS on perception of noxious contact heat stimuli. Our findings indicate that TENS may be interacting segmentally to modulate distinct aspects of sensitization, which in turn results in analgesia to thermal stimulation.
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The Mediating Role of Acceptance in Multidisciplinary Cognitive-Behavioral Therapy for Chronic Pain.
Cognitive-behavioral therapy (CBT) is the most frequently delivered psychological intervention for adults with chronic pain. The treatment yields modest effect sizes, and the mechanisms of action remain understudied and unclear. Efforts are needed to identify treatment mediators that could be used to refine CBT and improve outcomes. The primary aim of this study was to investigate whether pain-related acceptance, from the psychological flexibility model, mediates changes in outcome over time in a CBT-based treatment program. This includes comparing how this variable relates to 3 other variables posited as potential mediators in standard CBT: life control, affective distress, and social support. Participants attended a 5-week outpatient multidisciplinary program with self-report data collected at assessment, posttreatment, and 12-month follow-up. Multilevel structural equation modeling was used to test for mediation in relation to 3 outcomes: pain interference, pain intensity, and depression. Results indicate that effect sizes for the treatment were within the ranges reported in the CBT for pain literature. Pain-related acceptance was not related to pain intensity, which is in line with past empirical evidence and the treatment objectives in acceptance and commitment therapy. Otherwise, pain-related acceptance was the strongest mediator across the different indices of outcome. Accumulated results like these suggest that acceptance of pain may be a general mechanism by which CBT-based treatments achieve improvements in functioning. More specific targeting of pain-related acceptance in treatment may lead to further improvements in outcome. ⋯ Potential mediators of outcome in a CBT-based treatment for adult chronic pain were investigated using multilevel structural equation modeling. The results highlight the role of pain-related acceptance as an important treatment process even when not explicitly targeted during treatment. These data may help clinicians and researchers better understand processes of change and improve the choice and development of treatment methods.