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Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain.

Study Design: Systematic Review and Meta-analysis. Objective: The purpose of this study was to evaluate whether transcranial motor evoked potential (TcMEP) alarms can predict postoperative neurologic complications in patients undergoing cervical spine decompression surgery. Methods: A meta-analysis of the literature was performed using PubMed, Web of Science, and Embase to retrieve published reports on intraoperative TcMEP monitoring for patients undergoing cervical spine decompression surgery. The sensitivity, specificity, and diagnostic odds ratio (DOR), of overall, reversible, and irreversible TcMEP changes for predicting postoperative neurological deficit were calculated. A subgroup analysis was performed to compare anterior vs posterior approaches. Results: Nineteen studies consisting of 4608 patients were analyzed. The overall incidence of postoperative neurological deficits was 2.58% (119/4608). Overall TcMEP changes had a sensitivity of 56%, specificity of 94%, and DOR of 19.26 for predicting deficit. Reversible and irreversible changes had sensitivities of 16% and 49%, specificities of 95% and 98%, and DORs of 3.54 and 71.74, respectively. In anterior procedures, TcMEP changes had a DOR of 17.57, sensitivity of 49%, and specificity of 94%. In posterior procedures, TcMEP changes had a DOR of 21.01, sensitivity of 55%, and specificity of 94%. Conclusion: TcMEP monitoring has high specificity but low sensitivity for predicting postoperative neurological deficit in cervical spine decompression surgery. Patients with new postoperative neurological deficits were 19 times more likely to have experienced intraoperative TcMEP changes than those without new deficits, with irreversible TcMEP changes indicating a much higher risk of deficit than reversible TcMEP changes. [ABSTRACT FROM AUTHOR]

Flexor tendon injuries of the hand, especially in zone II, pose a challenge for hand surgeons because of the region's intricate pulley mechanism and local avascularity, and post-surgical complications such as repair failure are not uncommon. One proposed predictor of outcomes following flexor tendon repair has been timing of surgery from initial injury. However, the effect of the timing of flexor tendon repair on failure rates remains controversial and understudied. The purpose of this study was to compare the failure rates of zone II flexor tendon repairs in patients at various time intervals from onset of injury. A retrospective chart review was conducted using data from hand surgery specialists at our level 1 trauma center from January 1, 2010, through May 31, 2020. This retrospective review included 407 zone II flexor tendon repairs. The primary outcome was failure of repair. Among 407 flexor tendon repairs, there were 12 reported repair failures. The failure rate was 2.9%. In the non-failure group, the mean number of days between the date of injury and the date of surgery was 7±13 days. For the failure group, this value was 14±17 days. Repairs occurring within 14 days had a failure rate of 2.3%, while repairs occurring beyond 14 days had a failure rate of 7.7%. This study demonstrates that there is a benefit to repairing the tendon within a 14-day window, as evidenced by a lower failure rate. More research is required to determine if other complications and overall health of the hand are also improved when a repair is performed in a more expedient manner. [Orthopedics. 2024;47(2):113–117.] [ABSTRACT FROM AUTHOR]