The effects of gabapentin in human experimental pain models☆

Abstract 

Background

The antidepressant drugs imipramine and venlafaxine relieve clinical neuropathic pain and have been shown to increase pain thresholds in healthy volunteers during repetitive electrical sural nerve stimulation causing temporal pain summation, whereas pain during the cold pressor test is unaltered by these drugs. If this pattern of effect in experimental pain models reflects potential efficacy in clinical neuropathic pain, the pain summation model may potentially be used to identify new drugs for such pain conditions. Gabapentinoids are evidence-based treatments of clinical neuropathic pain and could contribute with additional knowledge of the usefulness of the pain summation model.

The aim of this study

To test the analgesic effect of the gabapentinoid gabapentin in a sural nerve stimulation pain model including temporal pain summation and the cold pressor test.

Method

18 healthy volunteers completed a randomized, double-blind, cross-over trial with medication of 600mg gabapentin orally dosed 3 times over 24h against placebo. Pain tests were performed before and 24h after medication including pain detection and tolerance to single sural nerve stimulation and pain summation threshold to repetitive stimulation (3Hz). Peak pain intensity and discomfort were rated during a cold pressor test.

Results

Compared to placebo, gabapentin had a highly significant effect on the threshold of pain summation to repetitive electrical sural nerve stimulation (P=0.009). Gabapentin significantly increased the pain tolerance threshold to single electrical sural nerve stimulation (P=0.04), whereas the pain detection threshold to single electrical sural nerve stimulation tended to be increased (P=0.06). No significant differences were found on pain ratings during the cold pressor test.

Conclusion

Gabapentin had a selective hypoalgesic effect in a human experimental pain model of temporal pain summation and the results lend further support to the usefulness of the pain summation model to identify drugs for neuropathic pain.

Keywords: Human experimental pain model, Neuropathic pain, Electrical nerve stimulation, Temporal summation, Cold pressor test, Gabapentin