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

Abstract

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.

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…Five of the nine studies examined local anesthetics in several surgical populations [12][13][14][15][16], one study compared a tumor necrosis factor-alpha (TNF-a) inhibitor (i.e., enteracept) for inguinal hernia compared to placebo [17], another study compared pregabalin versus placebo in a cardiac surgery model [18], and another study examined minocycline (a broad-spectrum cycline antibiotic which has been shown to block microglial activation) compared to placebo following lumbar discectomy [19]. These eight trials were negative and did not demonstrate a preventive analgesic effect [12][13][14][15][16][17][18][19]. Only one of the nine studies identified in our updated literature search found a preventive effect on the incidence of CPSP [20].…”

“…The heterogeneity with respect to the timing of interventions, the time points studied, and the outcomes assessed limit meaningful comparison of CPSP trials to date .There were two negative trails identified in this review which focused on minocycline [19] and entanercept [17] as possible agents that may play a role in modifying the transition from an acute pain to chronic pain. The role of tumor necrosis factor-alpha (TNF-a) inhibitors and medications implicated in the blocking of microglial activation deserve further study.…”

Prevention of chronic pain after surgery: new insights for future research and patient care

“…36 A recent example of attempts to prevent chronic pain with a ''non-analgesic'' intervention comes from a placebo-controlled trial of oral minocyclinean inhibitor of microglial activation expected to suppress central sensitization -administered for eight days perioperatively in lumbar discectomy patients. 37 Unfortunately, minocycline did not produce significant pain reductions at three months postoperatively; however, since all patients had pain prior to surgery, it must be acknowledged that this trial was conducted in likely the most challenging population for prevention. 37 It is possible that such neuroprotective agents may show even more impressive preventive efficacy when administered perioperatively to patients with no preexisting pain.…”

“…37 Unfortunately, minocycline did not produce significant pain reductions at three months postoperatively; however, since all patients had pain prior to surgery, it must be acknowledged that this trial was conducted in likely the most challenging population for prevention. 37 It is possible that such neuroprotective agents may show even more impressive preventive efficacy when administered perioperatively to patients with no preexisting pain. These concepts provide new opportunities for research and treatment with different classes of potentially preventive interventions.…”

“…36 Un exemple récent de tentatives de prévention de la douleur chronique à l'aide d'une intervention 'non analgésique' est tiré d'une étude contrôlée par placebo portant sur la minocycline orale -un inhibiteur de l'activation des microglies dont on prévoit qu'il supprimera la sensibilisation centrale -administrée durant huit jours avant la chirurgie chez les patients subissant une discectomie lombaire. 37 Malheureusement, la minocycline n'a pas réduit de manière significative la douleur à trois mois après la chirurgie; toutefois, étant donné que tous les patients souffraient de douleur avant la chirurgie, il faut tenir compte du fait que cette étude a été menée dans la population où la prévention était probablement la plus difficile à réaliser. 37 Il est possible que de tels agents neuroprotecteurs montrent une efficacité de prévention encore plus impressionnante lorsqu'ils sont administrés en périopératoire à des patients ne souffrant pas de douleur auparavant.…”