Articles: hyperalgesia.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine.
Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia. ⋯ A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.
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Comparative Study
Application of nucleus pulposus to L5 dorsal root ganglion in rats enhances nociceptive dorsal horn neuronal windup.
Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly through a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses, but it is unknown whether this reflects a central or peripheral sensitization. To study central sensitization, we tested if NP enhances windup--the progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation--a phenomenon that may partly account for temporal summation of pain. ⋯ These results are consistent with NP-induced central sensitization. Mechanical responses were not significantly enhanced after saline or NP treatment. We speculate that inflammatory agents released from (or recruited by) NP affect the dorsal root ganglion (and/or are transported to cord) to enhance primary afferent excitation of nociceptive dorsal horn neurons.
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Comparative Study
Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with a new model in the hairy skin of the rat.
An incision of hairy skin of the rat's back provides a new model for postincisional pain to determine the importance of cutaneous anesthesia. ⋯ Incision of rat hairy skin changes pain responses, similar to pain in humans. Preincisional subcutaneous bupivacaine selectively suppresses and shortens allodynia for times far outlasting its local anesthesia, an effect largely from systemic actions.
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Abnormal spontaneous firing is well described in axotomized sensory neurons and likely contributes to nerve injury-induced pain. The hyperpolarization-activated current I(h) initiates spontaneous, rhythmic depolarization in the sinoatrial node and central neurons. This study was undertaken to investigate the possible contribution of I(h) to primary afferent ectopic discharge and pain behavior in nerve-injured rats. Nerve injury was produced by tight ligation of lumbar spinal nerves (L5/6). Two weeks later, rats showed marked mechanical allodynia. Withdrawal thresholds were measured before and after administration of saline or the specific I(h) antagonist ZD7288 (1, 3, or 10 mg/kg, intraperitoneally). ZD7288 dose-dependently reversed mechanical allodynia. In a second experiment, we performed both in vivo and in vitro extracellular single unit recordings from teased dorsal root fascicles. Intravenous infusion (2.5 or 5 mg/kg) of ZD7288 during a period of 10 minutes significantly blocked ectopic discharges in vivo. Perfusion (25 to 100 mumol/L) of ZD7288 for 5 minutes in vitro almost completely blocked ectopic discharges from large myelinated fibers (Abeta) while partially suppressing ectopic discharge from thinly myelinated fibers (Adelta). We conclude from these data that in axotomized sensory neurons, a ZD7288-sensitive current contributes to spontaneous discharges in myelinated fibers. Thus, I(h) might substantially contribute to the pathophysiology of nerve injury-related neuropathic pain. ⋯ The current study investigated the mechanism of abnormal spontaneous discharges (ectopic discharges) from axotomized sensory afferents. Ectopic discharges are a main driving source of nerve injury-induced neuropathic pain. Understanding the mechanism of ectopic discharges and identifying how to control them will be useful toward developing new therapies.
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Although epinephrine (EPI) has been suggested to contribute to the pain and hyperalgesia associated with inflammation and nerve injury, there have been very few in vivo electrophysiologic studies of the effects of EPI on nociceptors. We found with the single-unit recording technique that the intradermal administration of EPI resulted in excitation of a group of C fibers and a decrease in the mechanical activation threshold in a non-overlapping group. Unexpectedly, the fibers that were neither excited nor demonstrated a decrease in threshold demonstrated as a group a significant increase in response to sustained suprathreshold mechanical stimuli, an effect not observed in the other 2 groups of C fibers. This identifies a novel response of C-fiber nociceptors to an inflammatory mediator and suggests it is present in a class of C fibers previously considered unresponsive to hyperalgesic inflammatory mediators. ⋯ Our study provides support for the suggestion that EPI, a neuroendocrine stress hormone as well as an inflammatory mediator, might contribute to pain syndromes, especially in the setting of chronic stress.