title: Transient tactile allodynia following intrathecal puncture in mouse: contributions of Toll-like receptor signaling.
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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0818, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Stokes
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D003433:Crosses, Genetic; D004388:Dura Mater / Q000293:injuries*; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal / Q000009:adverse effects*; D007530:Isoflurane / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology; D010812:Physical Stimulation; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000503:physiopathology; D013623:Tail; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D014110:Touch / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018685:Anesthetics, Inhalation; D007530:Isoflurane; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse