Articles: hyperalgesia.
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Pain hypersensitivity is a cardinal sign of tissue damage, but how molecules from peripheral tissues affect sensory neuron physiology is incompletely understood. Previous studies have shown that activin A increases after peripheral injury and is sufficient to induce acute nociceptive behavior and increase pain peptides in sensory ganglia. This study was designed to test the possibility that the enhanced nociceptive responsiveness associated with activin involved sensitization of transient receptor potential vanilloid I (TRPV1) in primary sensory neurons. ⋯ Pharmacological studies revealed that the activin sensitization of capsaicin responses required PKCepsilon signaling, but not PI3K (phosphoinositide 3-kinase), ERK (extracellular signal-regulated protein kinase), PKA, PKCalpha/beta, or Src. Furthermore, activin administration caused acute thermal hyperalgesia in wild-type mice, but not in TRPV1-null mice. These data suggest that activin signals through its own receptor, involves PKCepsilon signaling to sensitize the TRPV1 channel, and contributes to acute thermal hyperalgesia.
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Physiology & behavior · Dec 2007
Behavioural, histological and cytokine responses during hyperalgesia induced by carrageenan injection in the rat tail.
We produced experimental inflammatory hyperalgesia by injecting carrageenan into the tail of Sprague-Dawley rats. We compared the rats' voluntary running wheel activity following carrageenan injection into the tail to that after carrageenan injection into the hind paw, the conventional site of inflammation, to identify whether the site of inflammatory-induced hyperalgesia altered voluntary activity. We also measured voluntary running before and after injection of carrageenan or saline into the tail or hind paw, and in separate groups of rats we measured the nociceptive response and the associated pro-inflammatory cytokine profiles following a carrageenan injection into the tail. ⋯ Both thermal and mechanical hyperalgesia were present after carrageenan injection into the tail (P<0.01, ANOVA). The hyperalgesia at the site coincided with significant increases in TNF-alpha, IL-1beta, IL-6 and CINC-1 tissue concentrations, peaking 6 h after carrageenan injection (P<0.01, ANOVA). We conclude that carrageenan injection into the tail produces inflammatory hyperalgesia with underlying pro-inflammatory cytokine release, but does not affect voluntary running wheel activity in rats.
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Anesthesia and analgesia · Dec 2007
Comparative StudySecondary hyperalgesia in the postoperative pain model is dependent on spinal calcium/calmodulin-dependent protein kinase II alpha activation.
Spinally administered non-N-methyl-D-aspartate (NMDA), but not NMDA, receptor antagonists block primary (1 degree) and secondary (2 degrees) mechanical hyperalgesia and spontaneous pain after plantar incision. Hyperalgesia after thermal stimulation is also mediated by non-NMDA, but not NMDA, receptors. Although previous pain behavior studies in the thermal stimulus model demonstrated distinct protein kinase involvement downstream from spinal non-NMDA receptor activation, protein kinase signaling mechanisms have not been examined in the postoperative pain model. In the present study, we investigated whether spinal calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) mediates 1 degree and/or 2 degrees hyperalgesia and spontaneous pain behavior after plantar incision. ⋯ Spinal sensitization underlying incision-evoked hyperalgesia involves spinal CaMKIIalpha activation and enhanced spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA) function.
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Anesthesia and analgesia · Dec 2007
Case ReportsA differential diagnosis of hyperalgesia, toxicity, and withdrawal from intrathecal morphine infusion.
Opioid-induced hyperalgesia, toxicity, and withdrawal are phenomena that may occur with intrathecal opioid infusion. We present a case in which a patient received intrathecal morphine infusion, and then experienced a clinical course that may have involved hyperalgesia, toxicity, and/or withdrawal. The possible differential diagnosis of opioid-induced hyperalgesia, toxicity, and withdrawal, and its implications in clinical pain management, are discussed. This report demonstrates the complexity of treating patients with long-term continuous intrathecal opioids when modest adjustment of the intrathecal cocktail results in a paradoxical clinical course.
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Severe burn induces severe pain. While chronic as well as acute pain syndromes are reported, the peripheral mechanisms of burn-induced chronic pain syndromes have not been studied. We tested the hypothesis that burn induces plastic changes in primary afferent nociceptors that predispose to chronic pain states. ⋯ After recovery, local injection of prostaglandin E2 (PGE2), to mimic re-injury, induced an enhanced and markedly prolonged mechanical hyperalgesia compared to the hyperalgesic effect of PGE2 in the control contralateral paw. This prolonged PGE2-induced hyperalgesia was reversed by a selective inhibitor of protein kinase C-epsilon (PKCepsilon). Our findings suggest PKCepsilon as a peripheral mechanism for burn-induced chronic pain syndromes.