The journal of pain : official journal of the American Pain Society
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Pretreatment with intraperitoneal (i.p.) indomethacin was used to determine whether indomethacin preferentially affected the development of edema and hyperalgesia to thermal and mechanical stimuli produced by injection of zymosan in the ispsilateral hindpaw of the rat. Indomethacin also was delivered intrathecally (i.t.) either 30 minutes before or 4 hours after intraplantar zymosan to determine whether spinal prostaglandin production was important for the induction and/or maintenance of hyperalgesia. Zymosan alone produced a robust edema, a monophasic mechanical hyperalgesia, and a biphasic thermal hyperalgesia in the ipsilateral hindpaw. ⋯ Once hyperalgesia was established, i.t. indomethacin also attenuated the mechanical hyperalgesia whereas it had no effect on thermal hyperalgesia or edema. These data suggest that peripheral, but not spinal prostaglandins contribute to the edema and development of thermal hyperalgesia produced by zymosan. In contrast, spinal prostaglandins contribute to the development and maintenance of mechanical hyperalgesia.
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Intraplantar formalin injection produces early (Phase 1, 0- to 5-minute) and late (Phase 2, 15-plus minutes after injection) nociceptive responses, including painlike behavior and activation of primary afferents and dorsal horn neurons. Although we and others have reported that opioid analgesia or local anesthesia during Phase 1 does not reduce the overall magnitude of behavioral and/or neuronal responses during Phase 2, recent studies concluded that spinal sensitization during Phase 1 significantly contributes to the magnitude of painlike behavior during Phase 2. In this article, we provide additional evidence that Phase 1 and Phase 2 behaviors are independent. ⋯ We suggest that Phase 1 behaviors compared with Phase 2 behaviors in the formalin test are not an appropriate model of spinal sensitization or preemptive opioid analgesia. Instead, early opioid administration delayed the onset of edema produced by formalin. Because the antiedema effect of remifentanil was reversed with a peripherally acting opioid receptor antagonist, we suggest that opioids interact with peripheral receptors to temporarily delay the onset and offset of formalin-induced edema.
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The purpose of this research trial is to assess the effectiveness and tolerability of tizanidine in neuropathic pain. In an open-label study, patients with neuropathic pain received 1 to 4 mg of tizanidine once daily for 7 days, followed by weekly dose escalation of 2 to 8 mg to his/her effective or maximum tolerated dose or a maximum of 36 mg over an 8-week period. Treatment effects were assessed, using average weekly pain scores as well as biweekly scores for patient global assessment of pain relief, the neuropathic pain scale, and wisconsin brief pain inventory. ⋯ Tizanidine might be an effective treatment for neuropathic pain, offering an alternative for patients poorly responsive to other medications. A larger, randomized placebo-controlled trial is recommended. In addition, comparative studies with alternative agents should be sought.
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The relationship between joint pain and hyperalgesia has been explored in animal models of articular inflammation, but is yet to be shown in the most common rheumatologic condition: osteoarthritis. In this study, cutaneous thermal and mechanical pain thresholds were measured over the thumb of patients with osteoarthritis of the hands. In symptomatic patients, pain was manipulated through resisted active movement of the thumb. ⋯ Increased mechanical sensitivity after exacerbation of MP was alleviated by A beta fiber blockade. It appears that superficial tenderness over the osteoarthritic thumb fluctuates with pain arising from movement of the joint. It is concluded that dorsal horn mechanisms contribute to MP-related hyperalgesia in osteoarthritis of the hands.
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Given that transcutaneous electrical nerve stimulation (TENS) achieves its anti-hyperalgesia through endogenous opioid receptors, this study was undertaken to assess if TENS in combination with morphine was more effective at reducing primary hyperalgesia. Acute inflammation was induced by subcutaneous injection of 3% carrageenan into the rat's hindpaw. The withdrawal latency to heat and the mechanical withdrawal threshold were assessed before and after inflammation and after treatment with TENS (high- or low-frequency). ⋯ In combination with morphine, low-frequency TENS produced a similar reduction in mechanical hyperalgesia when compared with morphine alone. High-frequency TENS in combination with morphine produced a similar reduction in mechanical hyperalgesia when compared with the effects of high-frequency TENS alone. Thus, a lower dose of morphine could be used in combination with TENS to decrease the side effects of systemic morphine and achieve the same degree of analgesia.