Extraterritorial Heat Hyperalgesia in Mice Following Infraorbital Nerve Transection

Extraterritorial Heat Hyperalgesia in Mice Following Infraorbital Nerve Transection Mariam Mashregi Doctor of Philosophy Faculty of Dentistry University of Toronto 2017 Abstract Orofacial nerve injuries often lead to long-lasting pain which, is frequently perceived outside the field of injury (extraterritorial pain) and continues long after healing is complete. It has been suggested that sex and genetic factors may contribute to the development of neuropathic pain. These aspects were addressed in the present dissertation by first assessing nociceptive responses to noxious radiant heat stimuli in healthy male and female mice of the AXB-BXA recombinant inbred panel (A/J and C57BL/6J parental strains and their 23 descendant strains), and then comparing baseline responses to nociceptive responses following unilateral infraorbital nerve transection (IONX) or sham surgery, in the ears, ventral and dorsal tail, and hind-paws. These body sites were extraterritorial to the field innervated by the infraorbital nerve. Strain differences in heat hyperalgesia were utilised as phenotypes for genetic linkage analysis to identify chromosomal regions harbouring candidate genes. Since heat absorption depends on skin pigmentation, and the 25 strains were comprised of black, agouti (light-brown/taupe), and white coat colours, a standard heat intensity that elicited a threshold withdrawal at each body site was determined for each coat colour group and used for subsequent studies. Significant body-site-specific and strain-specific differences in baseline heat nociception were found, however, no sex differences were noted except in the ventral tail (male > female). Sensitisation to repeated noxious stimulation within the same test session was also noted in all body sites tested. Following surgery (IONX and sham), significant heat hyperalgesia was seen in many strains in all tested body sites. Sex differences were seen only in the ventral tail (female > male). The same post-operative increases were seen in both the sham and IONX groups, which might be explained by surgery-induced neuritis. Narrow-sense heritability estimates for baseline heat nociception and post-operative extraterritorial heat hyperalgesia ranged from 0.09 to 0.49 (in all body sites). Suggestive (but not significant) quantitative trait loci were mapped for baseline heat nociception in chromosomes 3,7,9, and 13 and for post-operative heat hyperalgesia in chromosomes 4, 11, and X. Several candidate genes were identified in these suggestive regions thus, necessitating future research to identify the causative genes.Ph.D.2018-11-30 00:00:0