Pain
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The degree to which neuropathic and non-neuropathic pain conditions differ in psychological and psychosocial status remains largely unexplored. A better understanding of these aspects would be of considerable benefit in helping to define whether similar psychological treatment strategies (eg, cognitive-behavioural therapy) can be adopted in the management of neuropathic pain as in non-neuropathic pain conditions. Chronic orofacial pain disorders present a unique opportunity to compare nociceptive and neuropathic pain in the same body region. ⋯ Although patients with trigeminal neuropathic pain (neuropathic pain) and temporomandibular disorder (non-neuropathic pain) described the sensory aspects of their pain differently, they exhibited comparable negative affective-motivational, cognitive-evaluative, and psychosocial states, although these were significantly different compared to healthy controls. These findings support growing evidence that the negative affective, cognitive, and psychosocial state of chronic pain is universal, regardless of a neuropathic or nociceptive nature. Further characterisation of these 4 dimensions of the pain experience in different chronic pain subtypes may improve the efficacy of cognitive-behavioural therapy.
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Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both peripheral nociceptors and the spinal cord. Genetic knockdown and knockout experiments have shown that specific channel isoforms, including Na(V)1.7 and Na(V)1.8 sodium channels and Ca(V)3.2 T-type calcium channels, play distinct pronociceptive roles. We have rationally designed and synthesized a novel small organic compound (Z123212) that modulates both recombinant and native sodium and calcium channel currents by selectively stabilizing channels in their slow-inactivated state. ⋯ In vivo experiments demonstrate that oral administration of Z123212 is efficacious in reversing thermal hyperalgesia and tactile allodynia in the rat spinal nerve ligation model of neuropathic pain and also produces acute antinociception in the hot-plate test. At therapeutically relevant concentrations, Z123212 did not cause significant motor or cardiovascular adverse effects. Taken together, the state-dependent inhibition of sodium and calcium channels in both the peripheral and central pain signaling pathways may provide a synergistic mechanism toward the development of a novel class of pain therapeutics.
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Neuropathic pain is a severe health problem for which there is a lack of effective therapy. A frequent underlying condition of neuropathic pain is a sustained overexcitability of pain-sensing (nociceptive) sensory fibres. Therefore, the identification of mechanisms for such abnormal neuronal excitability is of utmost importance for understanding neuropathic pain. ⋯ Behavioural experiments demonstrated that neuropathic hyperalgesia following PSNL developed faster than the downregulation of Kcnq2 expression could be detected, suggesting that this transcriptional mechanism may contribute to the maintenance rather than the initiation of neuropathic pain. Importantly, the decrease in the peripheral M channel abundance could be functionally compensated by peripherally applied M channel opener flupirtine, which alleviated neuropathic hyperalgesia. Our work suggests a novel mechanism for neuropathic overexcitability and brings focus on M channels and REST as peripheral targets for the treatment of neuropathic pain.
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Acupuncture is commonly used for pain control, but doubts about its effectiveness and safety remain. This review was aimed at critically evaluating systematic reviews of acupuncture as a treatment of pain and at summarizing reports of serious adverse effects published since 2000. Literature searches were carried out in 11 databases without language restrictions. ⋯ Serious adverse effects continue to be reported. Numerous reviews have produced little convincing evidence that acupuncture is effective in reducing pain. Serious adverse events, including deaths, continue to be reported.
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Pain of both neuropathic and nociceptive aetiology is common after spinal cord injury (SCI), and classifying pain is sometimes a challenge. The objective of this study was to test the usefulness of the Swedish version of the screening tools Douleur Neuropathique 4 questions (DN4), the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), the Neuropathic Pain Questionnaire (NPQ), and the painDETECT Questionnaire (PD-Q) in individuals with SCI and pain. A further objective was to define pain descriptors able to discriminate neuropathic pain from nonneuropathic pain. ⋯ LANSS and NPQ demonstrated the highest specificity (100%), followed by PD-Q (83%) and DN4 (75%). Diagnostic accuracy for the tools was for DN4 88%, PD-Q 78%, NPQ 65%, and LANSS 55%. A final model showed that 3 items, hypoesthesia to touch, burning pain, and numbness, could discriminate pain in this cohort of individuals with SCI with a high goodness of fit.