TNFα in MS and Its Animal Models: Implications for Chronic Pain in the Disease

Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.

Incidence and Risk Factors for Chronic Postsurgical Pain Following Video-assisted Thoracoscopic Surgery: a Retrospective Study

Backgroud: Video-assisted thoracoscopic surgery (VATS) has been widely used as an alternative for thoracotomy, but the reported incidence of chronic postsurgical pain (CPSP) following VATS varied widely. The purpose of this study was to investigate the incidence and risk factors for CPSP after VATS. Methods: We retrospectively collected preoperative demographic, anesthesiology, and surgical factors in a cohort of patients undergoing VATS between January 2018 and October 2020. Patients were interviewed via phone survey for pain intensity, and related medical treatment 3 months after VATS. Univariate and multivariate analysis were used to explore independent risk factors associated with CPSP.Results: 2,348 patients were included in our study. The incidence of CPSP after VATS were 43.99% (n = 1,033 of 2,348). Within those suffering CPSP, 14.71% (n = 152 of 1,033) patients reported moderate or severe chronic pain. Only 15.23% (n = 23 of 152) patients with moderate to severe chronic pain sought active analgesic therapies. According to multivariable analysis, age ＜ 65 years (OR 1.278, 95% CI 1.057-1.546, P = 0.011), female (OR 1.597, 95% CI 1.344-1.898, P < 0.001), education level less than junior school (OR 1.295, 95% CI 1.090-1.538, P = 0.003), preoperative pain (OR 2.564, 95% CI 1.696-3.877, P < 0.001), consumption of rescue analgesia postoperative (OR 1.248, 95% CI 1.047-1.486, P = 0.013), consumption of sedative hypnotic postoperative (OR 2.035, 95% CI 1.159-3.574, P = 0.013), subcutaneous emphysema of chest wall postoperative (OR 1.255, 95% CI 1.000-1.575, P = 0.050), and history of postoperative wound infection (OR 5.949, 95% CI 1.344-1.898, P < 0.001) were independent risk factors for CPSP development.Conclusions: CPSP remains a challenge in clinic because half of patients may develop CPSP after VATS. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100045765), 2021/04/24

The impact of the treatment of chronic pain treatment with transdermal buprenorphine on functional performance and risk of falls in elderly people diagnosed with osteoarthritis

The aim of the study was to evaluate the impact of transdermal buprenorphine on overall functional fitness and the risk for falls in the treatment of chronic pain in elderly patients diagnosed with osteoarthritis. Transdermal buprenorphine was used for 10 days in 60 patients over 64 years old in the treatment of severe chronic pain caused by osteoarthritis. Patients were randomly assigned to 3 groups with a starting dose of 8.75 µg/h, 17.5 µg/h, and 35 µg/h, respectively. On day 1 of the study, the Barthel Index, Instrumental Activities of Daily Living (IADL), Mini–Mental State Examination (MMSE), and the Tinetti balance and gait test were used. On the final day of the study, the Tinetti balance and gait test and the Barthel Index were used again. Pain intensity was evaluated every day with the Brief Pain Inventory – Short Form. No differences in IADL scores between patient groups in baseline assessment were found. An improvement in the Barthel Index overall scores was obtained in all patients with no differences between patient groups. An improvement for both balance and gait in all patient groups of the Tinetti test was found. Regarding balance and overall results, a more significant improvement in group 3 compared to groups 1 and 2 was observed. Transdermal buprenorphine provided satisfactory analgesia regardless of the starting dose of the drug with better toleration of lower initial doses: 8.75 µg/h and 17.5 µg/h compared to a starting dose of 35 µg/h. The treatment of elderly patients with severe chronic pain induced by osteoarthritis with different initial doses of transdermal buprenorphine improved overall physical fitness and reduced the risk for falls. The treatment resulted in satisfactory analgesia with less adverse effects in patients who started with lower initial lower doses of transdermal buprenorphine.

Dramatic Response to Lidocaine Infusion for Pain from Brachial Plexus Avulsion Injury

BACKGROUND: Traumatic brachial plexus avulsion injury (tBPI) can cause a severe chronic pain syndrome that is very difficult to treat. Though lidocaine has been shown to be effective for other pain syndromes, effectiveness in tBPI has not previously been reported. CASE REPORT: A 55-year-old man with tBPI had severe pain and minimal relief with numerous analgesic agents. He was able to access intravenous lidocaine as he was being treated at a cancer center, and had a sustained response to 7 mg/kg given over an hour. CONCLUSION: There is potential for a single bolus intravenous lidocaine infusion to provide good pain control sustained over many months in patients with traumatic brachial plexus injury. An adequate serum concentration of lidocaine is required for analgesic effect. If initial doses of lidocaine are tolerated but ineffective, higher doses may still be beneficial. KEY WORDS: Brachial plexus avulsion, lidocaine, lignocaine, pain management, palliative care, therapeutics, trauma