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Comparison of reflex and operant assays of cold vs mechanical testing in rat bilateral sciatic chronic constrictive injury (bCCI) model of neuropathic pain

Sukdeb Datta, MD, Anesthesiology, VA TVHS and Vanderbilt University, 1310 24th Avenue, South, Nashville, TN 37212-2637, Robert H. Kline, BS, Neurology, VA TVHS and Vanderbilt University, 1310 24th Avenue, South, Nashville, TN 37212-2637, Koel Chattejee, PhD, Experimental Neurology, Middle Tennessee Research Institute, 1310 24th Avenue, South, Nashville, TN 37212-2637, and Ronald G. Wiley, MD, PhD, Neurology and Pharmacology, VA TVHS and Vanderbilt University, 1310 24th Avenue, South, Nashville, TN 37212-2637.

Better unbiased animal models of neuropathic pain are needed that predict therapeutic efficacy and elucidate pathobiology. bCCI avoids asymmetric postural/motor influences of unilateral CCI and is more suitable for operant testing. Based on a recent report of prolonged increases in operant escape from cold in bCCI rats, the current project seeks to determine the time course, extent and reliability of changes in response to cold in simple reflex and operant assays compared to standard mechanical stimuli in the bCCI model. Two groups of Sprague Dawley rats were tested - initially three male older rats (mean age 18 months, mean body weight 515 gms.) with bCCI and one age-matched male control and then a second group of eight female rats (n=4 sham and n= 4 bCCI; mean age 4 months; mean body weight 252 gms.) were tested for 37 days. bCCI was produced by loose ligation of both sciatic nerves using three snug chromic gut sutures. Cold sensitivity was assessed by thermal plate testing at 0.3 C, acetone application to the dorsal surface of hindpaws and an operant place preference task using 0.3 C vs 45 C. Mechanical paw withdrawal thresholds were assessed using an electronic von Frey hair. Cold plate lick/guard responses peaked at 10-30 days. Flinching responses to acetone peaked at 9-15 days. Avoidance of cold in the place preference task peaked at 9-17 days. None of the cold responses returned to baseline. Mechanical withdrawal responses peaked at day 14 and returned to control baseline by day 23. Cold responses, both reflex and operant, are more robust and long lasting than mechanical responses in the bilateral CCI model of neuropathic pain. Thus, we conclude the bCCI model using precisely controlled cold stimuli offers advantages over the standard von Frey hair mechanical testing.