Porcine Acellular Nerve-Derived Hydrogel Improves Outcomes of Direct Muscle Neurotization in Rats.

Background: The ability to reinnervate a muscle in the absence of a viable nerve stump is a challenging clinical scenario. Direct muscle neurotization (DMN) is an approach to overcome this obstacle; however, success depends on the formation of new muscle endplates, a process, which is often limited due to lack of appropriate axonal pathfinding cues. Objective: This study explored the use of a porcine nerve extracellular matrix hydrogel as a neuroinductive interface between nerve and muscle in a rat DMN model. The goal of the study was to establish whether such hydrogel can be used to improve neuromuscular function in this model. Materials and Methods: A common peroneal nerve-to-gastrocnemius model of DMN was developed. Animals were survived for 2 or 8 weeks following DMN with or without the addition of the hydrogel at the site of neurotization. Longitudinal postural thrust, terminal electrophysiology, and muscle weight assessments were performed to qualify and quantify neuromuscular function. Histological assessments were made to qualify the host response at the DMN site, and to quantify neuromuscular junctions (NMJs) and muscle fiber diameter. Results: The hydrogel-treated group showed a 132% increase in postural thrust at 8 weeks compared with that of the DMN alone group. This was accompanied by an 80% increase in the number of NMJs at 2 weeks, and 26% increase in mean muscle fiber diameter at 8 weeks. Conclusions: These results suggest that a nerve-derived hydrogel may improve the neuromuscular outcome following DNM.

Divergent functions of the left and right central amygdala in visceral nociception.

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.