Objective To investigate the effect of intrathecal
ketamine on the intracellular calcium ion concentration
1 in the
spinal dorsal root ganglion (DRG) neurons in a rat model of chronic neuropathic pain produced by chronic constrictive injury (CCI) .Methods Thirty-six male SD rats weighing 160-180 g were randomly divided into 3 groups ( n = 12 each) : Ⅰ sham-operated group; Ⅱ CCI group and Ⅲ ketamine + CCI group. The animals were anesthetized with intraperitoneal pentobarbital 40 mg·kg-1 . The right sciatic nerve was exposed and 4 loose ligatures were placed on the trunk of the nerve at 1-2 mm interval. In sham-operated group (Ⅰ) the sciatic nerve was exposed but not ligated. Intrathecal catheter was implanted at L4,5 and correct placement was confirmed by aspiration of cerebro-spinal fluid. In group Ⅲ ketamine 1 mg · kg-1 was administered intrathecally. 30 min before and on the 1st, 2nd, 3rd, 5th, 7th, 9th and 11th day after operation. In group Ⅰ and Ⅱ normal saline (NS) was given intrathecally instead of ketamine. Thermal and mechanical hyperalgesia were measured with ice-cold water and von-Frey filaments on the 7th and 14th day after operation. The animals were killed by cervical dislocation on the 7th (n = 6) and 14th ( n = 6) day. Bilateral DRG of L4-6 spinal nerve were removed and homogenized and centrifuged at 5 000 r/min. DRG neurons were isolated and < Ca2+ > i was measured by flow cytometry.Results In group Ⅱ (CCI) pain threshold to von-Frey hair stimulation decreased by 80.3% (on the 7th day) and 84.8% (14th day) while pain threshold to noxious thermal stimulation increased by 309.4% (the 7th day) and 336.2% (14th day) (P < 0.01) as compared to sham-operated group ( Ⅰ ) . In group Ⅲ (ketamine + CCI group) Ppain threshold to von-Frey hair stimulation decreased by 24.1% (the 7th day) and 52.7% (the 14th day) while pain threshold to cold water stimulation increased by 78.8% and 100.0% respectively compared to group Ⅰ . The differences in pain threshold between the groups were statistically significant. In group Ⅱ (CCI) the i in DRG neurons increased by 71.7% and 17.6% on the 7th and 14th day after operation on the left side and by 75.4% and 165.8% respectively on the operated side compared to group Ⅰ (sham-operated); whereas in group Ⅲ (ketamine + CCI) the i in DRG neurons increased by 19.1% and 5.7% on the left side and 23.6% and 63.9% on the operated side compared to group Ⅰ .Conclusion The antinociceptive effect of intrathecal ketamine may be associated with NMDA receptor and suppression of increases in i in the DRG neurons.