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Treatment of Pain and Hyperalgesia Due to Sensory Neuron Injury Using B-Vitamins in the Rat



Treatment of Pain and Hyperalgesia Due to Sensory Neuron Injury Using B-Vitamins in the Rat



Anesthesiology Abstracts of Scientific Papers Annual Meeting ( ): Abstract No A-949



B-vitamins such as thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12), have been demonstrated to be clinically useful in the treatment of various painful conditions such as lumbago, sciatica, trigeminal neuralgia, facial paralysis and optic neuritis as an analgesia adjuvant as well as those caused by obvious vitamin deficiencies. However, antinociceptive efficacy of B-vitamins has not been evaluated in animals with neuropathic pain due to the primary sensory neuron injury. To provide experimental evidence in support of the clinical use of the B-vitamins in aiding in the treatment of chronic pain due to nerve or neuron injury, the present study examined the antinociceptive effects of B-vitamins in rats with chronic compression of dorsal root ganglion (CCD, Song et al. 1999) and chronic constriction injury of the sciatic nerve (CCI, Bennett and Xie 1988). Experiments were performed on adult, male SD rats (n=76). Surgery was done under anesthesia induced by sodium pentobarbital (40 mg/Kg, i.p.). CCD was mimicked by surgically implanting stainless steel rods unilaterally into the intervertebral foramen. CCI was produced by loose ligation of the left sciatic nerve at the mid-thigh region with 4-0 chronic gut ligature. Thermal hyperalgesia was determined by significantly shortened latency of foot withdrawal to heat stimulation of the plantar surface of hindpaw (Hargreaves test, 1988). Complex B-vitamins (CBV) was intraperitoneally injected (i.p.) on the 3rd day after surgery for testing its short-term effects or continuously for 7 days from the day of surgery for examining its long-term effect. The results showed that B1 (33 mg/kg), B6(33 mg/kg), or B12 (0.5 mg/kg), (B1+B12) and (B1+B6+B12) significantly inhibited thermal hyperalgesia in CCD- and CCI- rats. The inhibition started within 30 min after injection and lasted for at 6-24 hours. Repetitive administration of B1+B12 or B1+B6 +B12 for 1 or 2 weeks produced long-term inhibitory effects on thermal hyperalgesia. Hyperalgesia was inhibited 40-70% during first two weeks, and then completely disappeared in 5-6 weeks. In contrast, thermal hyperalgesia lasted for apprx7-9 weeks in CCD- or CCI- rats with treatment of saline. These treatments did not change latency of foot withdrawal to heat stimulation in the side contralteral to injury and that in control rats. The present studies demonstrate that B-vitamins can reduce severity and duration of hyperalgesia following primary sensory neuron injury in rats. These results support and broaden clinical use of B-vitamins in the treatment of chronic pain due to similar injuries of the nervous system in humans. Anesthesiology 2003; 99: A949.

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