Responses of spinothalamic tract neurons to mechanical and thermal stimuli in an experimental model of peripheral neuropathy in primates

An experimental peripheral neuropathy (EPN) was induced in three monkeys (Macaca fascicularis) by ligation of spinal nerve L₇. Behavioral responses to innocuous mechanical stimuli were tested before and after the surgery. Two weeks after the nerve ligation, the activity of spinothalamic tract (STT) neurons was recorded on both sides of the spinal cord with the animal under general anesthesia. Responses of the STT neurons to the following stimuli applied to the skin were recorded: graded mechanical stimuli (brush, press, pinch, and squeeze), von Frey filaments of different bending forces (0.077- 19.05 g), 5-s heat stimuli ranging from 39 to 53°C, and 15 s cold stimuli (32-8°C). Innocuous mechanical stimulation of the foot did not evoke hindlimb withdrawal in the animals before surgery. Within 24-48 h after nerve ligation, the animals showed hindlimb withdrawal to the same innocuous stimuli. This behavior was more pronounced on the side of the ligation than on the sham-operated side and more frequent during the second week after the surgery. Responses of 51 STT neurons recorded on the side of the ligation (EPN all group) were compared with responses of 33 STT cells recorded on the sham-operated side (control group) and with records from STT neurons in unoperated animals obtained earlier (reference group). Neurons from the EPN all group were divided into two sets according to their rostrocaudal location (EPN R, rostral to L(6/7) border, n = 40; EPN C, caudal to L(6/7) border, n = 11). Neurons from the EPN all and EPN R groups had significantly higher background frequencies than those from the control and reference groups. Innocuous brush stimuli evoked mean discharge frequencies of ~35 Hz in EPN R neurons and only ~15 Hz in both control and reference groups. Increased responsiveness of EPN R neurons to innocuous stimuli was also demonstrated by lower thresholds and higher discharge frequencies to von Frey filament stimulation and by discriminative analysis of the responses evoked by graded mechanical stimuli. The responses of the EPN R neurons to heat stimulation of the skin showed decreased thresholds and increased responses to suprathreshold stimuli, resulting in a significant leftward shift of the stimulus-response curve compared with both reference and control groups. The neurons from the control group showed responses comparable to reference group values. Neurons from the reference group tested with the cooling stimuli showed no evoked response above background. In contrast to this, ~65% of the EPN R neurons showed cooling-evoked responses significantly different from both the reference and control groups, with a threshold of ~28°C. The responsiveness to cooling of the control group was similar to that of the reference group. Neurons from the EPN C group had, in general, weak responses to all stimuli tested. The low responsiveness of these neurons most likely reflects their peripheral deafferentation by the L₇ spinal nerve ligation. Our results strongly suggest that tight ligation of spinal nerve L₇ in monkeys results in behavioral and electrophysiological changes that parallel symptoms found in humans with chronic neuropathic pain-mechanical allodynia, thermal hyperalgesia, cold allodynia, and probably spontaneous pain. Possible mechanisms of these changes found in this model of peripheral neuropathy are discussed.