Substance P release from knee joint afferent terminals: modulation by opioids.

Perfusate obtained from the intra-articular space of the knee (100 microliters/min) in the halothane-anesthetized cat under resting conditions shows no detectable substance P-like immunoreactivity (SP-LI: less than 2 pg/20 min). Antidromic activation by electrical stimulation of the sciatic nerve at stimulus intensities which evoke activity in A beta/A delta/C but not A beta fibers or the local administration of capsaicin (10(-4) M) into the intra-articular perfusate results in a stimulus-dependent increase in the levels of SP-LI in the perfusate. This release is diminished in a naloxone-(1 mg/kg, i.v.) reversible fashion by sufentanil, D-Ala2-D-Leu5-enkephalin, and D-Pen2-D-Pen5-enkephalin, but not by U50488H (10(-4) M) added to the intra-articular perfusate. These observations thus suggest that the peripheral stores of SP-LI in small primary afferents are subject to release by antidromic activity and this release is subject to modulation by mu/delta receptors on these peripheral terminals.