Inhibition by Spinal μ- and δ-Opioid Agonists of Afferent-Evoked Substance P Release

• DOI: 10.1523/jneurosci.0252-05.2005
• Publication Date: 2005-04-06T19:43:18Z
• Authors: Ichiro Kondo; Juan Carlos G. Ma...; Bingbing Song; Frances Salgado; Simone Codeluppi; Xiao-Ying Hua; Tony L. Yaksh
• Keywords: DAMGO; Internalization; Tachykinin receptor 1

Opioid μ- and δ-receptors are present on the central terminals of primary afferents, where they thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when used neurokinin 1 receptor (NK1R) internalization as an indicator substance P release, Trafton et al. (1999) noted that this evoked was altered only modestly morphine delivered intrathecally at cord segment S1-S2. We reexamined issue studying effect opiates NK1R in slices vivo . In slices, dorsal root stimulation C-fiber intensity abolished μ agonist [ d -Ala 2 , N -Me-Phe 4 Gly-ol 5 ]-enkephalin (DAMGO) (1 m ) decreased δ -Phe 2,5 (DPDPE) ). hindpaw compression induced ipsilateral laminas I-II. significantly reduced (60 nmol), DAMGO DPDPE (100 but not κ trans -(1 S ,2 )-3,4-dichloro- -mathyl- -[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 L2 using intrathecal catheters. These doses agonists were equi-analgesic measured a thermal escape test. Lower neither nor inhibited internalization. contrast, percutaneous injections S1-S2 had modest escape, even higher doses. Morphine after systemic delivery, dose greater than necessary produce equivalent analgesia. All effects reversed naloxone. results indicate lumbar noxious stimuli-induced release from afferents confirmed behaviorally analgesic.