Articles: hyperalgesia.
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In vivo experiments using a rat model of painful facet joint distraction. ⋯ Results suggest ligament tension may be required to produce pain from facet joint loading. Further studies of other cellular responses are needed to define the mechanisms of painful facet joint injury.
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Recently, we have reported that melittin, a major toxic peptide of the whole bee venom, plays a central role in production of local inflammation, nociception and hyperalgesia following the experimental honeybee's sting. However, the exact peripheral mechanisms underlying melittin-induced multiple pain-related behaviors are still less characterized. In the present study, we sought to investigate the potential roles of peripheral mitogen-activated protein kinases (MAPKs) in melittin-induced nociception and hyperalgesia by pre- and post-administration of three MAPK inhibitors, namely U0126 (1 mug, 10 mug) for extracellular signal-regulated kinase (ERK), SP600125 (10 mug, 100 mug) for c-Jun N-terminal kinase (JNK) and SB239063 (10 mug, 100 mug) for p38 MAPK, into the local inflamed area of one hind paw of rats. ⋯ Furthermore, local administration of the three compounds in naïve animals, respectively, did not change the basal pain sensitivity to either thermal or mechanical stimuli, suggesting lack of peripherally functional roles of the three MAPK subfamily members in normal pain sensitivity under the physiological state. Taken together, we conclude that activation of peripheral MAPKs, including ERK, JNK and p38, might contribute to the induction and maintenance of persistent ongoing pain and primary heat hyperalgesia in the melittin test. However, they are not likely to be involved in the processing of melittin-induced primary mechanical hyperalgesia, implicating a mechanistic separation between mechanical and thermal hyperalgesia in the periphery.
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Although it has been shown that pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) facilitate perception of noxious inputs at the spinal level, the mechanisms have not been understood. This study determined the cell type that produces IL-1beta, the co-localization of IL-1 receptor type I (IL-1RI) and Fos and NR1 in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NR1 phosphorylation and hyperalgesia in a rat model of inflammatory pain. Phosphorylation of NR1, an essential subunit of the NMDA receptor (NMDAR), is known to modulate NMDAR activity and facilitate pain. ⋯ Spinal cords were removed for double immunostaining of IL-1beta/neuronal marker and IL-1beta/glial cell markers, IL-1RI/Fos and IL-1RI/NR1, and for Western blot to measure NR1 phosphorylation. The data showed that: (1) astrocytes produce IL-1beta, (2) IL-1RI is localized in Fos- and NR1-immunoreactive neurons within the spinal dorsal horn, and (3) IL-1ra at 0.01mg/rat significantly increased PWL (P<0.05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain.
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Randomized Controlled Trial
Pharmacological dissection of the paradoxical pain induced by a thermal grill.
We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. ⋯ By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.