Abstract
Studies of spinal drug action in mice often involve percutaneous intrathecal drug administration delivered in a lightly anesthetized animal. A successful lumbar intrathecal (IT) needle stick of a lightly anesthetized (isoflurane) mouse evokes a tail flick, which is an indication of local spinal nerve stimulation. Immediately upon arousal, a hind paw tactile allodynia, as measured with von Frey hairs (pre 1.55±0.11 g vs. injected 0.66±0.08 g) lasts 3-4 h. In a similarly anesthetized mouse without the needle stick, a 1-h allodynia was noted. In studies on spinal Toll-like receptor (TLR) signaling, we observed that following intrathecal puncture and mechanical stimulation of the nerve roots mice deficient in TLR down-stream signaling (Myd88(-/-)/Trif(lps2)), displayed only the transient (1-h) allodynia otherwise observed following isoflurane alone. These data suggest that the extended period of hyperalgesia observed with needle penetration of the dura and mechanical stimulation of the nerve roots requires signaling through the MyD88/TRIF pathways and supports the intrinsic role of Toll-like receptors in the allodynia secondary to the minor nerve activation occurring during the intradural puncture.