Articles: hyperalgesia.
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Water immersion is widely used in physiotherapy and might relieve pain, probably by activating several distinct somatosensory modalities, including tactile, pressure, and thermal sensations. However, the endogenous mechanisms behind this effect remain poorly understood. This study examined whether warm water immersion therapy (WWIT) produces an antiallodynic effect in a model of localized inflammation and whether peripheral opioid, cannabinoid, and adenosine receptors are involved in this effect. ⋯ WWIT produced a significant time-dependent reduction of paw inflammatory allodynia but did not influence paw edema induced by CFA. Naloxone, caffeine, DPCPX, and AM630 injected in the right, but not in the left, hind paw significantly reversed the antiallodynic effect of WWIT. This is the first study to demonstrate the involvement of peripheral receptors in the antiallodynic effect of WWIT in a murine model of persistent inflammatory pain.
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Toxicol. Mech. Methods · Jan 2015
3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury.
There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed. ⋯ LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.
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We have recently shown that the prolongation of prostaglandin E2 hyperalgesia in a preclinical model of chronic pain-hyperalgesic priming-is mediated by release of cyclic adenosine monophosphate from isolectin B4-positive nociceptors and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn, acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously showed that antisense against an extracellular matrix molecule, versican, which defines the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation of prostaglandin E2 hyperalgesia. To further evaluate the mechanisms at the interface between the extracellular matrix and the nociceptor's plasma membrane involved in hyperalgesia prolongation, we interrupted a plasma membrane molecule involved in versican signaling, integrin β1, with an antisense oligodeoxynucleotide. Integrin β1 antisense eliminated mechanical hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine, in the primed rat. We also disrupted a molecular complex of signaling molecules that contains integrin β1, lipid rafts, with methyl-β-cyclodextrin, which attenuated the prolongation without affecting the acute phase of prostaglandin E2 hyperalgesia, while having no effect on cyclopentyladenosine hyperalgesia. Our findings help to define the plasma membrane mechanisms involved in a preclinical model of chronic pain. ⋯ The present study contributes to a further understanding of mechanisms involved in the organization of messengers at the plasma membrane that participate in the transition from acute to chronic pain.
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A transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors can produce long-lasting neuroplastic changes in nociceptor function, eventually enhancing and prolonging inflammatory hyperalgesia. Here, we investigated the effects of selective α2-adrenoceptor agonist dexmedetomidine (DMED) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). The ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli decreased significantly starting from 24 h after ischemia-reperfusion (I/R) injury, and lasted for over 3 weeks; the ipsilateral cold allodynia scores, GRK2 protein and mRNA levels in SCGs all increased significantly. ⋯ Following daily injection of 10 μg/kg of DMED for a maximum of 7 days, the ipsilateral PWTs on days 1, 2, 7, 14, and 21 after DMED administration were significantly higher than those in control group; the GRK2 protein and mRNA expressions in the ipsilateral SCGs were also significantly upregulated; the ipsilateral cold allodynia scores were significantly reduced. No significant differences were found in the contralateral 50%PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly on days 1 to 7 after DMED administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and DMED might alleviate this allodynia through GRK2 upregulation in SCG neurons.
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We investigated the capacity of intrathecal arachidonyl-2'-chloroethylamide (ACEA), a cannabinoid-1 receptor (CB1R) agonist, to inhibit referred hyperalgesia and increased bladder contractility resulting from acute acrolein-induced cystitis in rats. 24 female rats were divided into 4 groups: 1) intrathecal vehicle/intravesical saline; 2) intrathecal vehicle/intravesical acrolein; 3) intrathecal ACEA/intravesical saline; and 4) intrathecal ACEA/intravesical acrolein. Bladder catheters were placed 4-6 days prior to the experiment. On the day of the experiment, rats were briefly anesthetized with isoflurane to recover the external end of the cystostomy catheter. ⋯ Intrathecal ACEA prevented referred hyperalgesia associated with acute acrolein-induced cystitis. However, in this experimental model, ACEA did not ameliorate the associated urodynamic changes. These findings suggest that pain arising from cystitis may be inhibited by activation of spinal CB1R but the acute local response of the bladder appeared to be unaffected by stimulation of spinal CB1R.