Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents.
Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents.
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DOI：
10.1186/1744-8069-7-4
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发表时间：
2011-01-10
期刊：
影响因子：
3.3
通讯作者：
Porreca F
中科院分区：
文献类型：
--
作者：
Okun A;DeFelice M;Eyde N;Ren J;Mercado R;King T;Porreca F
组织损伤会引起对诱发刺激的超敏反应和持续的、与刺激无关的疼痛。我们之前证明，缓解疼痛可以给神经损伤的老鼠带来奖励。这种方法用于评估炎症引起的持续疼痛的时间和机械特征。足底内完全弗氏佐剂 (CFA) 产生热痛觉过敏和防护行为，在 24 小时内可靠地观察到，并在给药后 4 天维持（尽管有所减弱）。脊髓可乐定在 CFA 治疗的大鼠中产生强烈的条件性位置偏好 (CPP)，但在 CFA 给药后第 1 天，但不是第 4 天。然而，脊髓可乐定在 CFA 后第 1 天和第 4 天均阻断了 CFA 诱导的热痛觉过敏，表明持续疼痛和诱发疼痛的时间进程不同。足底 CFA 后 1 天，通过利多卡因注射到腘窝进行周围神经阻滞，产生了对利多卡因配对室的强烈偏好，表明损伤引起的持续疼痛是由支配损伤部位的传入纤维驱动的。用树脂毒素 (RTX) 进行预处理，RTX 是一种超强辣椒素类似物，已知可对 TRPV1 阳性传入神经产生持久脱敏作用，完全阻断 CFA 诱导的热超敏反应，并消除 CFA 后 24 小时给予腘窝利多卡因引起的 CPP。此外，RTX 预处理阻断了足底 CFA 后 1 天观察到的守卫行为。相比之下，以逆转 CFA 诱导的热痛觉过敏的剂量施用选择性 TRPV1 受体拮抗剂 AMG9810 未能减少 CFA 诱导的持续疼痛或防护行为。这些数据表明，炎症会引起持续的疼痛和诱发的超敏反应，这可以根据时间进程进行区分。持续的疼痛 (a) 是短暂的，(b) 由损伤引起的外周输入驱动，(c) 依赖于 TRPV1 阳性纤维，并且 (d) 不被 TRPV1 受体拮抗作用所阻断。损伤后早期这些传入纤维兴奋的机制将为创伤后早期开发新的疼痛缓解策略提供见解。
Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief elicits reward in nerve-injured rats. This approach was used to evaluate the temporal and mechanistic features of inflammation-induced ongoing pain. Intraplantar Complete Freund's Adjuvant (CFA) produced thermal hyperalgesia and guarding behavior that was reliably observed within 24 hrs and maintained, albeit diminished, 4 days post-administration. Spinal clonidine produced robust conditioned place preference (CPP) in CFA treated rats 1 day, but not 4 days following CFA administration. However, spinal clonidine blocked CFA-induced thermal hyperalgesia at both post-CFA days 1 and 4, indicating different time-courses of ongoing and evoked pain. Peripheral nerve block by lidocaine administration into the popliteal fossa 1 day following intraplantar CFA produced a robust preference for the lidocaine paired chamber, indicating that injury-induced ongoing pain is driven by afferent fibers innervating the site of injury. Pretreatment with resiniferatoxin (RTX), an ultrapotent capsaicin analogue known to produce long-lasting desensitization of TRPV1 positive afferents, fully blocked CFA-induced thermal hypersensitivity and abolished the CPP elicited by administration of popliteal fossa lidocaine 24 hrs post-CFA. In addition, RTX pretreatment blocked guarding behavior observed 1 day following intraplantar CFA. In contrast, administration of the selective TRPV1 receptor antagonist, AMG9810, at a dose that reversed CFA-induced thermal hyperalgesia failed to reduce CFA-induced ongoing pain or guarding behavior. These data demonstrate that inflammation induces both ongoing pain and evoked hypersensitivity that can be differentiated on the basis of time course. Ongoing pain (a) is transient, (b) driven by peripheral input resulting from the injury, (c) dependent on TRPV1 positive fibers and (d) not blocked by TRPV1 receptor antagonism. Mechanisms underlying excitation of these afferent fibers in the early post-injury period will offer insights for development of novel pain relieving strategies in the early post-traumatic period.
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影响因子：
14.5
作者：
KOLTZENBURG, M;TOREBJORK, HE;WAHREN, LK
通讯作者：
WAHREN, LK
影响因子：
4
作者：
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Brennan, Timothy J.
DOI：
10.1016/j.atc.2004.11.009
发表时间：
2005-03-01
期刊：
Anesthesiology clinics of North America
影响因子：
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作者：
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通讯作者：
Pogatzki-Zahn, Esther M
DOI：
10.1302/0301-620x.87b3.15694
发表时间：
2005-03-01
影响因子：
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作者：
Kadiyala, RK;Ramirez, A;Cassell, MD
通讯作者：
Cassell, MD
DOI：
10.1124/jpet.104.079855
发表时间：
2005-04-01
影响因子：
3.5
作者：
Gavva, NR;Tamir, R;Treanor, JJS
通讯作者：
Treanor, JJS