Articles: hyperalgesia.
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Korean J. Intern. Med. · Jun 2009
Effect of the combined use of tramadol and milnacipran on pain threshold in an animal model of fibromyalgia.
Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. ⋯ We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans.
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Proc. Natl. Acad. Sci. U.S.A. · May 2009
Suppressed Ca2+/CaM/CaMKII-dependent K(ATP) channel activity in primary afferent neurons mediates hyperalgesia after axotomy.
Painful axotomy decreases K(ATP) channel current (IK(ATP)) in primary afferent neurons. Because cytosolic Ca(2+) signaling is depressed in injured dorsal root ganglia (DRG) neurons, we investigated whether Ca(2+)-calmodulin (CaM)-Ca(2+)/CaM-dependent kinase II (CaMKII) regulates IK(ATP) in large DRG neurons. Immunohistochemistry identified the presence of K(ATP) channel subunits SUR1, SUR2, and Kir6.2 but not Kir6.1, and pCaMKII in neurofilament 200-positive DRG somata. ⋯ Axotomized neurons from rats made hyperalgesic by SNL lost sensitivity to the myristoylated form of autocamtide-2-related inhibitory peptide (AIPm), a pseudosubstrate blocker of CaMKII, whereas axotomized neurons from SNL animals that failed to develop hyperalgesia showed normal IK(ATP) inhibition by AIPm. AIPm also depolarized RMP in control neurons via K(ATP) channel inhibition. Unitary current conductance and sensitivity of K(ATP) channels to cytosolic ATP and ligands were preserved even after painful nerve injury, thus providing opportunities for selective therapeutic targeting against neuropathic pain.
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Randomized Controlled Trial
Medial prefrontal cortex activity is predictive for hyperalgesia and pharmacological antihyperalgesia.
Sodium channel blockers are known for reducing pain and hyperalgesia. In the present study we investigated changes in cerebral processing of secondary mechanical hyperalgesia induced by pharmacological modulation with systemic lidocaine. An experimental electrical pain model was used in combination with functional magnetic resonance imaging. ⋯ However, only activity in mPFC was inversely correlated to area of hyperalgesia during placebo and antihyperalgesic treatment effect. Furthermore, the difference of mPFC activity during hyperalgesia and placebo versus hyperalgesia and lidocaine correlated inversely with the change of the weighted hyperalgesic area (as a factor of area and rated pain intensity). We conclude that activity in mPFC correlates inversely with individual extent of central hyperalgesia and predicts individual pharmacological antihyperalgesic treatment response.
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The transient receptor potential vanilloid 4 (TRPV4) contributes to mechanical hyperalgesia of diverse etiologies, presumably as part of a mechanoreceptor signaling complex (Alessandri-Haber et al., 2008). To investigate the hypothesis that a functional interaction between TRPV4 and stretch-activated ion channels (SACs) is involved in this mechanical transduction mechanism, we used a selective SACs inhibitor, GsMTx-4. Intradermal injection of GsMTx-4 in the rat hindpaw reversed the mechanical hyperalgesia induced by intradermal injection of inflammatory mediators. ⋯ Spinal intrathecal administration of oligodeoxynucleotides antisense to TRPC1 and TRPC6, like that to TRPV4, reversed the hyperalgesia to mechanical and hypotonic stimuli induced by inflammatory mediators without affecting baseline mechanical nociceptive threshold. However, antisense to TRPC6, but not to TRPC1, reversed the mechanical hyperalgesia induced by a thermal injury or the TRPV4-selective agonist 4alpha-PDD (4 alpha-phorbol 12,13-didecanoate). We conclude that TRPC1 and TRPC6 channels cooperate with TRPV4 channels to mediate mechanical hyperalgesia and primary afferent nociceptor sensitization, although they may have distinctive roles.
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Opioids have been and continue to be used for the treatment of chronic pain. Evidence supports the notion that opioids can be safely administered in patients with chronic pain without the development of addiction or chemical dependency. However, over the past several years, concerns have arisen with respect to administration of opioids for the treatment of chronic pain, particularly non-cancer pain. ⋯ Tolerance is a necessary condition for OIH but the converse is not necessarily true. Office-based detoxification, reduction of opioid dose, opioid rotation, and the use of specific NMDA receptor antagonists are all viable treatment options for OIH. The role of sublingual buprenorphine appears to be an attractive, simple option for the treatment of OIH and is particularly advantageous for a busy interventional pain practice.