Articles: neuropathic-pain.
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Biochemical pharmacology · Oct 2015
The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain.
The aim of the present study was to determine the impact of α5 nicotinic acetylcholine receptor (nAChR) subunit deletion in the mouse on the development and intensity of nociceptive behavior in various chronic pain models. The role of α5-containing nAChRs was explored in mouse models of chronic pain, including peripheral neuropathy (chronic constriction nerve injury, CCI), tonic inflammatory pain (the formalin test) and short and long-term inflammatory pain (complete Freund's adjuvant, CFA and carrageenan tests) in α5 knock-out (KO) and wild-type (WT) mice. The results showed that paw-licking time was decreased in the formalin test, and the hyperalgesic and allodynic responses to carrageenan and CFA injections were also reduced. ⋯ Nicotine reversal of mechanical allodynia in the CCI test was mediated through α5-nAChRs at spinal and peripheral sites. In summary, our results highlight the involvement of the α5 nAChR subunit in the development of hyperalgesia, allodynia and inflammation associated with chronic neuropathic and inflammatory pain models. They also suggest the importance of α5-nAChRs as a target for the treatment of chronic pain.
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OBJECT Failed-back surgery syndrome has been historically used to describe extremity neuropathic pain in lumbar disease despite structurally corrective spinal surgery. It is unclear whether specific preoperative pain characteristics can help determine which patients may be susceptible to such postoperative disabling symptoms. METHODS This prospective study analyzed surgical microdiscectomy patients treated for lumbar, degenerative, painful radiculopathy. ⋯ CONCLUSIONS This population exhibited a low overall frequency of PPNP. Higher neuropathic pain screening scores correlated strongly with likelihood of significant postoperative leg pain. Further work is required to develop more accurate prognostication tools for radiculopathy patients undergoing structural spinal surgery.
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An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. ⋯ Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.
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High-intensity focused ultrasound (HIFU) is a non-invasive technique that allows a small, well-circumscribed thermal lesion to be generated within a tissue target. Tissue destruction occurs due to direct heating within the lesion and the mechanical effects of acoustic cavitation. HIFU has been used in a broad range of clinical applications, including the treatment of malignancies, uterine fibroids and cardiac arrhythmias. ⋯ The majority of studies conducted investigating the use of HIFU in pain are still at an early stage, although initial results are encouraging. Further research is indicated to improve our understanding of the mechanisms underlying this treatment and to fully establish its efficacy; however, it is likely that HIFU will play a role in pain management in the future. This narrative review provides a synthesis of the recent, salient clinical and basic science research related to this topic and gives a general introduction to the mechanisms by which HIFU exerts its effects.
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Up-regulation of voltage-gated calcium channel α2 δ1 subunit post spinal nerve ligation (SNL) injury or in α2 δ1 -overexpressing transgenic (Tg) mice correlates with tactile allodynia, a pain state mediated mainly by Aβ sensory fibres forming synaptic connections with deep dorsal horn (DDH) neurons. It is not clear, however, whether dysregulated α2 δ1 alters DDH synaptic neurotransmission that underlies tactile allodynia development post nerve injury. ⋯ Our data suggest that α2 δ1 dysregulation is highly likely contributing to tactile allodynia through a pre-synaptic mechanism involving facilitation of excitatory synaptic neurotransmission in DDH of spinal cord.