Upper-Extremity Peripheral Nerve Stimulators.

Chronic pain conditions are some of the most challenging problems upper-extremity surgeons face and often require a multimodal approach including neuromodulation. Peripheral nerve stimulation (PNS) is one of these modalities, delivering electrical stimulation to peripheral axons to modulate the spinal cord and block out nociceptive signals from the extremity. This blockade leads to long-lasting effects in both the peripheral and central nervous systems. Not only does PNS decrease peripheral pain signals but it also decreases the peripheral inflammatory response and assists with central nervous system plasticity for long-term pain control. Although PNS was initially developed in the 1960s, it has been underrepresented in the literature largely due to the advent of spinal cord stimulation and the lack of Food and Drug Administration-approved hardware for PNS. However, for upper-extremity pain, PNS provides notable benefits over spinal cord stimulation devices, as PNS allows for safer, more specific, and often more effective pain control. As clinicians attempt to limit narcotic use, therapies such as PNS have been revisited and are gaining popularity. We present a narrative review of PNS; discuss its mechanism of action, indications, and surgical technique; and provide a summary of the available literature for the upper-extremity surgeon. Peripheral nerve stimulation offers a solution for chronic, debilitating pain recalcitrant to other treatment modalities.

Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes.

Increasing evidence suggests that spinal microglia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain following intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID (a caspase-6 inhibitor) and the astroglial inhibitors L-α-aminoadipate (L-AA, an astroglial toxin) and carbenoxolone (a connexin 43 inhibitor), as well as U0126 (an ERK kinase inhibitor) and D-JNKI-1 (a c-Jun N-terminal kinase inhibitor). We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflammatory pain in both sexes. Intrathecal U0126 and D-JNKI-1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.