Sex-related differences in development of hyperalgesia induced by sciatic nerve ligation in mice

Introduction: In normal animals, neuro pathic pai n aris ing from scia tic nerve ligatio n injury ca n res ult in in cr e ase d se ns it ivity to bot h nox ious ( hy pe ra lges ia) a nd no n-n o xi o us s t imu li (a llodynia) and are accompanied by a num be r of ne uroplast ic alte rnations at the level of sp ina l cord incl uding upregu lat io n of neurotransmi tte rs including dynorp h in. neu ro pe p t id e Y a nd cholecystokini n. Some research studies have bee n sh own th at the mechanisms underlying ne uropath ic pain pr o ce ssi ng d if fe red as a fu nc t io n o f ge nde r a nd gon ada l hormone status . Howe ve r , th e effe ct of nerve injury o n ac ute no cicep ti on an d se x- re lated di ff'cr c nc c s in time-course o f hyperalgesia has not been exte nsive ly stud ied. Materials and Methods: A model of perip he ra l nerve in j u ry was used to st udy gend e r d iffere nces in the progression of chronic co nst ric t io n injury ind uced hype ra lge s ia in male and female mice. Nerve ligati o n injury was pro duced by un ilat eral ligation around th e le ft commo n sciatic nerve. Anima ls we re examined for response to acu te nocicep tio n daily during the thre e postoperative weeks. I n t his regard , the la te ncy o f t ail fli ck response (T F L) wa s me asured in co ntrol gro up and at se t intervals (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 days af te r sciat ic ligatio n as liga ted or surgery wi t hou t ligati o n as sham gro ups in bo t h sex e s ) by us in g a n a ut o ma ted an algesia me ter. Results: In the absence of ne rve inj ury. int act (8.4 ± O.95 Sec) and sham (8 .35 ± 0.3 Se c) males responded fast er tha n control (8.7 ± O.99 Sec) and sham (8. 9 ± O.34 Sec) fema les to a thermal nocice pt ive st imulus. Howeve r. the re were no sign ifica nt differences be tween gro ups and both sexes. Significant hyperalgesia was develo ped in ligat ed male and female mice , as compa re d to co n trol a nd sh am groups , wi th in 10 d ays afte r sc ia tic nerve injury (P< O. OI ). Howe ver, it el onga ted for six d ays in ma le s an d more tha t 10 d ays in fema les. On t he other hand, TFL in males (4.9±O.1 Sec) red uced significa ntly (P