Background: Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. Methods: Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L₆ transverse process; (2) ligated (Group L), which underwent left L₅ spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L₅ SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav_1.3 and Nav_1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD₃) and 7 (POD₇). Results: Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav_1.3 and down-regulation of Nav_1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD₃, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav_1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD₇ (p = 0.002). Conclusions: Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav_1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain.

Background: Amitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation (SNL)-induced neuropathic pain.Methods: 96 adult male Sprague–Dawley rats were allocated into 4 groups: groupS,Sham; groupL, L5 spinal nerveLigation with vehicle treatment; groupA, SNL and post-injury intra-peritoneal (Abdominal) amitriptyline twice daily × 3 days; groupP, intrathecalPretreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily × 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion (DRG) and activated glial cells in spinal dorsal horn (SDH) were measured pre-operatively and on post-operative day (POD) 4, 7, 14, 21 and 28.Results: SNL-evoked hyper-sensitivity responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14.Conclusions: Concomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes and dysregulated Nav1.3 and 1.8.

Adequate postoperative analgesia after hallux valgus (HV) correction surgery improves early mobilization and decreases hospital stay. Peripheral nerve block and peri‐incisional local anesthetic (LA) infiltration are both widely used for pain management in orthopedic surgeries. The aim of this study was to compare the analgesic effects between the ankle block and peri‐incisional infiltration technique in patients undergoing HV correction surgery. Ninety patients scheduled for hallux valgus correction surgery were randomly allocated into three groups. In group N, patients were pretreated with tibial and peroneal nerve blocks with 8‐10 mL of 0.25% bupivacaine before surgery. In group P, patients received the same LA for peri‐incisional infiltration preoperatively. In group C, patients underwent surgery without regional analgesic pretreatment. All patients had intravenous fentanyl patient control analgesia as part of multimodal postoperative pain management. Fentanyl consumption, rest and moving pain scale, and adverse effects were evaluated at postoperative 6 h (Poh6), Poh12, Poh 24, and Poh36, respectively. Patients receiving bilateral feet surgeries were excluded in this study. Seventy‐five patients were enrolled into final analysis. The patients in group N expressed lower resting and moving pain scores at Poh6, but the pain scores turned similarly among the three groups following Poh12 and then. The total fentanyl consumption was significantly less in group N than in group P. The postoperative activities and mood disturbance were not significantly different between groups after Poh12 and then. We conclude that ankle block is better than peri‐incisional LA infiltration in HV correction surgery in pain relief and fentanyl consumption.