Articles: hyperalgesia.
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J. Korean Med. Sci. · Nov 2012
Analgesic effects of dexmedetomidine in vincristine-evoked painful neuropathic rats.
Dexmedetomidine, which is a selective α2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. ⋯ Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 ± 0.4, 9.1 ± 1.9, 13.0 ± 3.6, 16.6 ± 2.4, and 24.4 ± 1.6 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 ± 4.2, 57.1 ± 6.8, 34.3 ± 5.7, 20.0 ± 6.2, and 14.3 ± 9.5 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).
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Neuroscience letters · Oct 2012
Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord.
The activation of α2-adrenoceptors has attracted attention as a therapeutic target for neuropathic pain, which remains a clinical challenge. In the present study, we examined the interaction between α2-adrenergic and cholinergic signaling in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intrathecal administration of dexmedetomidine, which is a selective α2-adrenoceptor agonist (0.1-1.0 μg), dose-dependently suppressed hyperalgesia in SNL rats but did not alter paw withdrawal thresholds in normal rats. ⋯ The combination of an ineffective dose of intrathecal dexmedetomidine with intraperitoneal donepezil, which is a cholinesterase inhibitor, decreased neuropathic hypersensitivity. These results suggest that plasticity of the spinal noradrenergic-cholinergic axis only occurs in neuropathic pain states. Thus, drug combinations that strengthen the noradrenergic-cholinergic interaction may provide therapeutic benefit in neuropathic pain.
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Injury or inflammation affecting sensory neurons in the dorsal root ganglia (DRG) causes hyperexcitability of DRG neurons that can lead to spinal central sensitization and neuropathic pain. Recent studies have indicated that, following chronic compression of DRG (CCD) or acute dissociation of DRG (ADD) treatment, both hyperexcitability of neurons in intact DRG and behaviorally expressed hyperalgesia are maintained by activity in cGMP-PKG signaling pathway. Here, we provide evidence supporting the idea that CCD or ADD treatment activates cGMP-PKA signaling pathway in the DRG neurons. ⋯ Hyperexcitability of the injured neurons is inhibited by cGMP-PKG pathway inhibitors, ODQ and Rp-8-pCPT-cGMPS. In vivo delivery of Rp-8-pCPT-cGMPS into the compressed ganglion within the intervertebral foramen suppresses CCD-induced thermal hyperalgesia. These findings indicate that the in vivo CCD or in vitro ADD treatment can activate the cGMP-PKG signaling pathway, and that continuing activation of cGMP-PKG pathway is required to maintain DRG neuronal hyperexcitability and/or hyperalgesia after these two dissimilar forms of injury-related stress.
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Our previous studies have shown that complete Freund's adjuvant (CFA)-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β) into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc) can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM), a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. ⋯ These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.
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Neuroscience letters · Oct 2012
P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice.
Ectopic pain in other orofacial regions develops with local inflammation in separated orofacial structures. However, the basis for the spreading of pain to adjacent orofacial areas after local inflammation is still unknown. In the present study, we determined if the P2X(3) receptor (P2X(3)R) was associated with altered mechanical sensitivity of the whisker pad skin following complete Freund's adjuvant (CFA) injection into the lower lip. ⋯ CGRP protein expression in TG ipsilateral to CFA injection was also significantly greater than that of the saline-injected mice. The present findings suggest that induced CGRP by local inflammation in the lower lip increases P2X(3)R in TG neurons, the increased P2X(3)Rs are involved in the sensitization of primary afferent neurons in the whisker pad skin. This P2X(3)R overexpression may underlie ectopic mechanical allodynia in the whisker pad skin after CFA injection into the lower lip.