Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, USA.
NanoAxis, LLC, Clarence, NY, USA.
Brain Behav Immun. 2019 Nov;82:93-105. doi: 10.1016/j.bbi.2019.07.036. Epub 2019 Jul 31.
Neuropathic pain is chronic pain that follows nerve injury, mediated in the brain by elevated levels of the inflammatory protein tumor necrosis factor-alpha (TNF). We have shown that peripheral nerve injury increases TNF in the hippocampus/pain perception region, which regulates neuropathic pain symptoms. In this study we assessed pain sensation and perception subsequent to specific targeting of brain-TNF (via TNF antibody) administered through a novel subcutaneous perispinal route. Neuropathic pain was induced in Sprague-Dawley rats via chronic constriction injury (CCI), and thermal hyperalgesia was monitored for 10 days post-surgery. On day 8 following CCI and sensory pain behavior testing, rats were randomized to receive perispinal injection of TNF antibody or control IgG isotype antibody. Pain perception was assessed using conditioned place preference (CPP) to the analgesic, amitriptyline. CCI-rats receiving the perispinal injection of TNF antibody had significantly decreased CCI-induced thermal hyperalgesia the following day, and did not form an amitriptyline-induced CPP, whereas CCI-rats receiving perispinal IgG antibody experienced pain alleviation only in conjunction with i.p. amitriptyline and did form an amitriptyline-induced CPP. The specific targeting of brain TNF via perispinal delivery alleviates thermal hyperalgesia and positively influences the affective component of pain. PERSPECTIVE: This study presents a novel route of drug administration to target central TNF for treatment of neuropathic pain. Targeting central TNF through perispinal drug delivery could potentially be a more efficient and sustained method to treat patients with neuropathic pain.
神经病理性疼痛是一种由神经损伤引起的慢性疼痛，在大脑中由炎症蛋白肿瘤坏死因子-α（TNF）的升高水平介导。我们已经表明，外周神经损伤会增加海马体/疼痛感知区域的 TNF，从而调节神经病理性疼痛症状。在这项研究中，我们评估了通过新型皮下脊柱旁途径给予靶向大脑-TNF（通过 TNF 抗体）后对疼痛感觉和感知的影响。通过慢性缩窄性损伤（CCI）在 Sprague-Dawley 大鼠中诱导神经病理性疼痛，并在手术后第 10 天监测热痛觉过敏。在 CCI 后第 8 天和感觉疼痛行为测试后，大鼠随机接受脊柱旁注射 TNF 抗体或对照 IgG 同种型抗体。使用条件性位置偏好（CPP）评估疼痛感知，对镇痛剂阿米替林进行 CPP。接受脊柱旁 TNF 抗体注射的 CCI 大鼠在第二天明显减轻了 CCI 引起的热痛觉过敏，并且没有形成阿米替林诱导的 CPP，而接受脊柱旁 IgG 抗体注射的 CCI 大鼠仅在与腹腔内阿米替林联合使用时才缓解疼痛，并形成了阿米替林诱导的 CPP。通过脊柱旁给药靶向大脑 TNF 可减轻热痛觉过敏，并对疼痛的情感成分产生积极影响。观点：本研究提出了一种新的药物给药途径，用于治疗神经病理性疼痛的中枢 TNF。通过脊柱旁药物输送靶向中枢 TNF 可能是治疗神经病理性疼痛患者的更有效和持续的方法。
