title: Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain.
abstract: Postoperative pain significantly impacts patient recovery. However, postoperative pain management remains suboptimal, perhaps because treatment strategies are based mainly on studies using inflammatory pain models. We used a recently developed mouse model of incisional pain to investigate peripheral and spinal mechanisms contributing to heat hyperalgesia after incision. Behavioral experiments involving TRPV1 KO mice demonstrate that, as previously observed in inflammatory models, TRPV1 is necessary for heat (but not mechanical) hyperalgesia after incision. However, in WT mice, neither the proportion of TRPV1 immunoreactive neurons in the DRG nor the intensity of TRPV1 staining in the sciatic nerve was different from that in controls up to 4 days after incision. This result was corroborated by immunoblot analysis of sciatic nerve in rats subjected to an incision, and is distinct from that following inflammation of the rat hind paw, a situation in which TRPV1 expression levels in sciatic nerve increases. In the absence of heat exposure, spinal c-Fos staining was similar between incised TRPV1 KO and WT mice. However, differences in c-Fos staining between heat exposed TRPV1 KO and WT mice after incision suggest that the incision-mediated enhancement of heat-evoked signaling to the spinal cord involves a TRPV1-dependent mechanism. Finally, heat hyperalgesia after incision was reversed by antagonism of spinal non-NMDA receptors, unlike inflammatory hyperalgesia, which is mediated via NMDA receptors . Thus, TRPV1 is important for the generation of thermal hyperalgesia after incision. Our observations suggest that all experimental pain models may not be equally appropriate to guide the development of postoperative pain therapies.
authors.affiliation: Departments of Anesthesiology and CCM, Johns Hopkins University, Baltimore, MD, USA Departments of Biological Chemistry and Neuroscience, Johns Hopkins University, Baltimore, MD, USA Department of Anesthesiology and Intensive Care Medicine, University of Muenster, Albert Schweitzer Str. 33, 48149 Muenster, Germany Dainippon Pharmaceuticals, Osaka, Japan.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Pogatzki-Zahn
authors.forename: Isao
authors.initials: I
authors.lastname: Shimizu
authors.forename: Michael
authors.initials: M
authors.lastname: Caterina
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020078:Neurogenic Inflammation / Q000378:metabolism* / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012867:Skin / Q000293:injuries / Q000294:innervation; D050916:TRPV Cation Channels
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D016760:Proto-Oncogene Proteins c-fos; D011810:Quinoxalines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate