Articles: hyperalgesia.
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While intense or highly arousing stressors have long been known to suppress pain, relatively mild or chronic stress can enhance pain. The mechanisms underlying stress-induced hyperalgesia (SIH) are only now being defined. The physiological and neuroendocrine effects of mild stress are mediated by the dorsomedial hypothalamus (DMH), which has documented connections with the rostral ventromedial medulla (RVM), a brainstem region capable of facilitating nociception. ⋯ However, not all neurons projecting from the DMH to the RVM contained CCK, and microinjection of the CCK2 receptor antagonist YM022 in the RVM did not interfere with SIH, suggesting that transmitters in addition to CCK play a significant role in this connection during acute stress. While the RVM has a well-established role in facilitation of nociception, the DMH, with its well-documented role in stress, may also be engaged in a number of chronic or abnormal pain states. Taken as a whole, these findings establish an anatomical and functional connection between the DMH and RVM by which stress can facilitate pain.
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The present study examined the roles of ventrolateral orbital cortex (VLO) 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptor subtypes in mediating 5-HT-induced antiallodynic actions in the rat spared nerve injury (SNI) pain model. Changes in paw withdrawal threshold (PWT) were measured using von-Frey filaments. ⋯ In addition, these antagonists applied alone to VLO did not influence allodynia. These results suggest that although 5-HT1-7 receptor subtypes in the VLO do not have a tonic modulatory action on the allodynia induced by SNI, they are involved in mediating the depression of the SNI allodynia produced by injection of 5HT into VLO.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2013
Activation of cannabinoid receptor 2 inhibits experimental cystitis.
Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells. We investigated whether treatment with the CB2 agonist GP1a alters severity of experimental cystitis induced by acrolein and referred mechanical hyperalgesia associated with cystitis. ⋯ The inhibitory effects of the CB2 agonist were prevented by the selective CB2 antagonist AM630 (10 mg/kg, sc). We further demonstrated the inhibitory effects of CB2 appear to be at least partly mediated by reducing bladder inflammation-induced activation of ERK1/2 MAPK pathway. The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.
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Neuroscience letters · May 2013
Role of spinal opioid receptor on the antiallodynic effect of intrathecal nociceptin in neuropathic rat.
The purpose of this study was to examine the effects of intrathecal nociceptin for neuropathic pain and determine the role of spinal opioid receptor types. Neuropathic pain was induced by ligation of L5 and L6 spinal nerves in male Sprague-Dawley rats. Several antagonists were intrathecally administered to evaluate the action mechanisms of nociceptin: nonselective opioid receptor antagonist (naloxone), μ opioid receptor antagonist (CTOP), δ opioid receptor antagonist (naltrindole) and κ opioid receptor antagonist (GNTI). ⋯ Intrathecal nociceptin increased the level of δ opioid receptor protein compared with that of nerve ligated rats, while the levels of μ, and κ opioid receptor proteins were unchanged. These results suggest that intrathecal nociceptin produced antiallodynic effect in spinal nerve ligation-induced neuropathic pain. All three types of spinal μ, δ, and κ opioid receptors were involved in the antiallodynic mechanism of nociceptin.
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Accumulating evidence suggests that chemokine C-C motif receptor 2 (CCR2) plays an important role in neuropathic pain. It has been shown that spinal CCR2 is upregulated in several neuropathic pain models and expressed by neuronal and glial cells in the spinal cord. In this study, we investigated the expression changes and cellular localization of spinal CCR2 in a rat model of bone cancer induced by Walker 256 cell inoculation. ⋯ Western blot and immunohistochemical analysis demonstrated that the expression of CCR2 in the spinal cord was significantly increased on day 6, 12, and 18 in BCP rats, with a peak on day 6. Furthermore, double immunofluorescence labeling indicated that CCR2 was expressed by both microglia and neurons in the spinal cord. These results suggest that CCR2 may be involved in the development of BCP, and that targeting CCR2 may be a new strategy for the treatment of BCP.