Articles: hyperalgesia.
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Pharmacol. Biochem. Behav. · May 2011
Formalin-induced long-term secondary allodynia and hyperalgesia are maintained by descending facilitation.
This work analyzes the role of cholecystokinin (CCK) receptors, dynorphin A₁₋₁₇ and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary allodynia and hyperalgesia in formalin-injected rats. Formalin injection (50 μL, 1%, s.c.) produced acute nociception (lasting 1 h) and long-term secondary allodynia and hyperalgesia in ipsilateral and contralateral hind paws (lasting 1-12 days). Once established, intra-RVM administration of lidocaine at day 6, but not at 2, reversed secondary allodynia and hyperalgesia in rats. ⋯ Moreover, intrathecal administration of dynorphin antiserum reversed, but was unable to prevent, secondary allodynia and hyperalgesia in both hind paws. These results suggest that formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord. In addition, data suggest that spinal dynorphin A₁₋₁₇ and CCK play an important role in formalin-induced secondary allodynia and hyperalgesia.
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Opioid-induced hyperalgesia (OIH) and tolerance are challenging maladaptations associated with opioids in managing pain. Recent genetic studies and the existing literature suggest the 5-hydroxytryptamine type 3 (5-HT3) receptor participates in these phenomena. The location of the relevant receptor populations and the interactions between the 5-HT3 system and other systems controlling OIH and tolerance have not been explored, however. We hypothesized that 5-HT3 receptors modulate OIH and tolerance, and that this modulation involves the control of expression of multiple neurotransmitter and receptor systems. ⋯ Morphine acts via a 5-HT3-dependent mechanism to support multiple maladaptations to the chronic administration of morphine. Furthermore, the use of 5-HT3 receptor antagonists may provide a new avenue to prevent or reverse OIH and tolerance associated with chronic opioid use.
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Neuroscience research · May 2011
A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain.
The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. ⋯ KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.
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Pain is evoked by noxious body stimulation or through negative emotional events and memories. There are several caveats to the simple proposition that pain and emotion are linked in the cingulate cortex (CG). In this study, we investigated whether mild noxious heat stimuli could affect the neuronal activity in the CG of rats with sciatic nerve ligation. ⋯ Under this condition, there were no significant changes in the levels of immediate-early genes such as c-fos, c-jun, JunB, and Fra1 in the CG between nerve-ligated and sham-operated rats. However, mild noxious heat stimuli under a neuropathic pain-like state produced a marked increase in the phosphorylated-c-jun (p-c-jun) immunoreactivity, which is commonly used to map neurons in the brain that can be activated after N-methyl-D-aspartate receptor activation. These findings raise the possibility that mild noxious heat stimuli under a peripheral nerve injury may increase the release of glutamate and promote its related postneuronal activity in the CG.
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Neuron glia biology · May 2011
Involvement of calcitonin gene-related peptide and CCL2 production in CD40-mediated behavioral hypersensitivity in a model of neuropathic pain.
The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro-nociceptive role after peripheral nerve injury upon its release from primary afferent neurons in preclinical models of neuropathic pain. We previously demonstrated a critical role for spinal cord microglial CD40 in the development of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity. Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral hypersensitivity. ⋯ Further, there was decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx. However, CGRP8-37 did not significantly affect spinal cord CCL2 production following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes to the maintenance of behavioral hypersensitivity following peripheral nerve injury in part through two distinct pathways, the enhancement of CGRP expression and spinal cord CCL2 production.