Clinical, histological, and biochemical predictors of postsurgical neuropathic pain.

Surgical nerve injury sometimes leads to chronic postsurgical neuropathic pain (CPSNP). The risk factors for this condition are not well understood. We prospectively assessed 46 patients scheduled for iliac crest bone harvest, 2 days (D2) and 3 months (M3) after surgery, to determine the time course of nerve fiber degeneration and expression of the TNF-α and NGF genes in skin punch biopsies. Mechanical and thermal detection and pain thresholds were evaluated at D2 and M3, by quantitative sensory testing. Skin punch biopsies were also obtained from the thighs ipsilateral and contralateral to iliac crest bone harvest. Intraepidermal nerve fiber density (IENFD) and cutaneous TNF-α and NGF gene expression were analyzed. Forty-five volunteers matched for age, sex, skin color were examined as controls. Chronic postsurgical neuropathic pain was defined as pain in an area of hypesthesia with a positive Douleur Neuropathique 4 questionnaire score. Overall, 73% (N = 32) of patients developed hypesthesia and 40% (N = 13) of these patients had developed CPSNP at M3. Quantitative sensory testing results, IENFD, and skin TNF-α and NGF gene expression at D2 and M3 did not differ between patients with and without CPSNP. However, in patients with CPSNP, burning, compression, and pain provoked by brushing were correlated with IENFD at M3, suggesting a possible association between partial nerve lesions and more intense CPSNP, than with total nerve lesion. Furthermore, preoperative pain and opioid use were higher in patients who developed CPSNP than in those without CPSNP. These findings suggest that the predictors of CPSNP development are clinical rather than histological or biochemical.

The efficacy of a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: a randomized, double-blind, controlled study.

Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. The minocycline group received 100mg minocycline orally, twice daily, beginning the evening before surgery and continuing for 8 days. The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months. Secondary outcomes were pain intensity on movement, the incidence of persistent pain and chronic neuropathic pain, back pain intensity at rest and on movement, and changes in Neuropathic Pain Symptom Inventory, Brief Pain Inventory, and Roland-Morris scores at 3 months. An intention-to-treat analysis was performed for patients assessed from the day before surgery to 3 months. The decrease in lower limb pain intensity was similar in the placebo and minocycline groups, both at rest -1.7 ± 1.6 vs -2.3 ± 2.4 and on movement -2.5 ± 2.1 vs -3.4 ± 2.9. The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.