Articles: neuralgia.
-
Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The α4β2 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of α4β2 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for α4β2 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain. Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) at α4β2 nAChRs that enhances agonist responses without activating receptors. We hypothesized that dFBr may enhance nicotine-induced antinociception. ⋯ α4β2 nAChRs are involved in pain modulation. dFBr, a PAM at α4β2 nAChRs, potentiates the nicotine response dose-dependently in neuropathic pain. Thus, the present results suggest that allosteric modulation of α4β2* nAChR may provide new strategies in chronic neuropathic pain.
-
Paclitaxel-induced neuropathic pain is a major dose-limiting side effect of paclitaxel therapy. This study characterises a variety of rat behavioural responses induced by intermittent administration of clinically formulated paclitaxel. 2 mg/kg paclitaxel or equivalent vehicle was administered intraperitoneally on days 0, 2, 4, and 6 to adult male Sprague-Dawley rats. Evoked pain-like behaviours were assessed with von Frey filaments, acetone, or radiant heat application to plantar hind paws to ascertain mechanical, cold, or heat sensitivity, respectively. ⋯ Spontaneous burrowing behaviour and nocturnal wheel running were significantly impaired on day 28, but not on day 7, indicating ongoing pain-like behaviour, rather than acute drug toxicity. This study comprehensively characterises a rat model of paclitaxel-induced peripheral neuropathy, providing the first evidence for ongoing pain-like behaviour, which occurs in parallel with maximal mechanical/cold hypersensitivity. We hope that this new data improve the face validity of rat models to better reflect patient-reported pain symptoms, aiding translation of new treatments to the clinic.
-
Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. ⋯ The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.
-
Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10, and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL) and acts on chemokine receptor CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known about CXCL9 and CXCL11 in the maintenance of neuropathic pain. ⋯ In addition, intrathecal injection of CXCL9 and CXCL11 did not produce hyperalgesia or allodynia behaviors, and neither of them induced ERK activation, a marker of central sensitization. Whole-cell patch clamp recording on spinal neurons showed that CXCL9 and CXCL11 enhanced both excitatory synaptic transmission and inhibitory synaptic transmission, whereas CXCL10 only produced an increase in excitatory synaptic transmission. These results suggest that, although the expression of CXCL9 and CXCL11 are increased after SNL, they may not contribute to the maintenance of neuropathic pain.
-
Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. ⋯ Sodium channel blocker doses used in certain pain syndromes are outlined with a call for further research to better understand their place in chronic pain management. Identification of sodium channel subtypes with links to specific pain conditions and the ability to target them hints at the potential for truly individualized therapy. Sodium channel inhibitors are underutilized on the basis of available evidence, and emerging research has identified this area as promising for additional clinical trials to better guide clinical practice.