Carlton S M, Zhou S, Kraemer B, Coggeshall R E
Department of Anatomy and Neurosciences, Marine Biomedical Institute, 301 University Boulevard, University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Neuroscience. 2003;120(2):499-508. doi: 10.1016/s0306-4522(03)00337-3.
Our hypothesis is that peripheral somatostatin (SRIF) has a role in counter-irritation-induced analgesia. Our paradigm involves the reduction of nociceptive behaviors produced by primary noxious stimuli (formalin or complete Freund's adjuvant [CFA] in the rat hind paw) by a counter-irritating stimulus (capsaicin [CAP] in the tail or muzzle). Activation of peripheral SRIF receptors is key since an SRIF receptor antagonist cyclo-somatostatin (c-SOM) and SRIF antibodies in the hind paw attenuate the counter-irritation-induced analgesia of both formalin and more persistent CFA nociception. Specificity of c-SOM is shown by reversal of its effects with octreotide, a SRIF analog. Injection of formalin in one hind paw and c-SOM in the other does not reduce the counter-irritation analgesia demonstrating local action of the c-SOM. Approximately 33% of peripheral sensory axons contain SRIF, which could release the peptide to activate SRIF receptors on cutaneous axons. Intraplantar naloxone has no effect on the counter-irritation analgesia indicating that SRIF is not activating opioid receptors. These results indicate that in addition to the classic central descending noxious inhibitory control systems that underlie counter-irritation-induced analgesia, there is a peripheral contribution arising from activation of SRIF receptors. Identifying a peripheral contribution of SRIF to mechanisms of counter-irritation analgesia offers opportunities for peripheral therapy.
我们的假设是外周生长抑素（SRIF）在对抗刺激诱导的镇痛中发挥作用。我们的实验模式包括通过对抗刺激（尾部或口鼻部注射辣椒素[CAP]）来减少由初级伤害性刺激（大鼠后爪注射福尔马林或完全弗氏佐剂[CFA]）所产生的伤害性行为。外周SRIF受体的激活是关键，因为在后爪注射SRIF受体拮抗剂环生长抑素（c-SOM）和SRIF抗体可减弱对抗刺激诱导的福尔马林镇痛以及更持久的CFA伤害感受。c-SOM的特异性通过其作用被生长抑素类似物奥曲肽逆转得以体现。在一只后爪注射福尔马林而在另一只后爪注射c-SOM并不会降低对抗刺激镇痛，这表明c-SOM具有局部作用。大约33%的外周感觉轴突含有SRIF，其可释放该肽以激活皮肤轴突上的SRIF受体。足底内注射纳洛酮对对抗刺激镇痛没有影响，这表明SRIF不会激活阿片受体。这些结果表明，除了作为对抗刺激诱导镇痛基础的经典中枢下行伤害性抑制控制系统外，还存在由SRIF受体激活引起的外周作用。确定SRIF在外周对抗刺激镇痛机制中的作用为外周治疗提供了机会。
