Articles: hyperalgesia.
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Beta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. ⋯ Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of β2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined β2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of β2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of β2-AR agonists to models of surgical injury.
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We aimed at evaluating the differential involvement of large myelinated Aβ-, small myelinated Aδ-, and unmyelinated C-fibers in patients with diabetic polyneuropathy and how they contribute to neuropathic pain. ⋯ Diabetic polyneuropathy mainly manifests as a mixed-fiber polyneuropathy, simultaneously involving Aβ-, Aδ-, and C-fibers. In most patients, neuropathic pain is distinctly associated with small-fiber damage. The evidence that the frequency of neuropathic pain does not differ across pure large-, pure small-, and mixed-fiber polyneuropathy, raises the possibility that in patients with pure large-fiber polyneuropathy nociceptive nerve terminal involvement might be undetected by standard diagnostic techniques.
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Ultrasound Med Biol · Dec 2020
Pulsed Ultrasound Remedies Post-thoracotomy Hypersensitivity and Increases Spinal Anti-inflammatory Cytokine in Rats.
The purpose of the experiment was to study the effect of pulsed ultrasound (PUS) on post-thoracotomy pain and local tissue temperature and to correlate the findings with the alteration in spinal anti-inflammatory and pro-inflammatory cytokines. Mechanical sensitivity, subcutaneous temperature and spinal interleukin-10 (IL-10), IL-6 or tumor necrosis factor-alpha (TNF-α) expression were examined in a rat model of experimental post-thoracotomy pain. Group 1 received a sham surgery where thoracotomy was performed except for rib retraction. ⋯ We concluded that mechanical hypersensitivity after TRR is postponed by PUS, and its effect continues for 3 wk. A PUS dose not increase local tissue temperature. The beneficial effect of PUS appears related to upregulation of spinal anti-inflammatory cytokine and downregulation of spinal pro-inflammatory cytokines.
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Neuroscience bulletin · Dec 2020
Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1.
Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. ⋯ Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.