Objective: To observe the effect of hyaluronidase on neuropathic pain in chronic constriction nerve injury (CCI) rats and analyze the possible mechanisms of acupoint-injection of hyaluronidase (a typical enzyme for decomposing extra-cellular matrical polysaccharide) for analgesia. Methods: A total of adult SD rats were randomly divided into control group (n=10) and treatment group (n=12). CCI pain model was established by ligating the left sciatic nerve loosely with gauge-4 chromic catgut. Silver chloride electrode was used to record the ectopic spontaneous discharges of the proximal filaments of the injured nerve 2 cm above the ligated site and the latency of foot withdrawal reaction to heat stimulation was detected with hot-plate test. After CCI

the injured sciatic nerve was taken out and cut into sections which were stained with periodic acid Schiff (PAS)-hematoxylin and eosin (HE) techniques. Results: In our experiments

the rate of ectopic spontaneous discharges of the nerve filament was significantly reduced by 50.9%±12.4% in 8 of the 12 CCI rats after applying hyaluronidase to the injured site but was not affected by application of normal saline or mechanical stimulation

suggesting an injured nerve discharge. Behavioral test for neuropathic pain indicated that heat hyperalgesia of CCI rats could be reduced by applying hyaluronidase to the CCI site. After CCI

the pain reaction (foot withdrawal) latency was delayed significantly. The difference values of the latency of foot withdrawal reaction between post- and pre-CCI on the 3 rd

6 th and 14 th day in experimental group were lower or significantly lower (14 th day

P<0.05) than those of control group

indicating that local application of hyaluronidase could prevent the development of heat hyperalgesia. Histological observation displayed disordered arrangement of nerve fibers with bigger irregular spaces among them

swelling of tissues

deposition of polysaccharide granules and abundant cellular neuclei among the fibers

indicating appearance of inflammation in the injured portion of the sciatic nerve. In hyaluronidase treated samples

no deposition of protein polysaccharide granules was found

the arrangement of nerve fibers and cellular nuclei were basically normal. Conclusion: Extra-cellular matrix has a close relation with neuro-physiological functions and hyaluronidase can effectively suppress CCI induced ectopic spontaneous discharges. It suggests that clinical application of acupoint-injection of hyaluronidase to change local extra-cellular matrix may have an analgesic effect on chronic pain.