Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) are essential for the survival of geniculate ganglion neurons, which provide the sensory afferents for taste buds of the anterior tongue and palate. To determine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BDNF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpression of BDNF or NT4 caused a 93 and 140% increase, respectively, in the number of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in the dorsal midregion and ventral tip of the tongue. No alterations were observed in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many were small, poorly innervated, and lost postnatally. To explain the loss of nerve innervation to fungiform papillae, the facial nerve of developing animals was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons in BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innervation to filiform papillae was observed. In addition, some papillae that formed in transgenic mice had two taste buds (instead of one) and were frequently arranged in clusters of two or three papillae. These results indicate that target-derived BDNF and NT4 are not only survival factors for geniculate ganglion neurons, but also have important roles in regulating the development and spatial patterning of fungiform papilla and targeting of taste neurons to these sensory structures.

Objective: The purpose of this study was to examine the overall prevalence of polypharmacy within the spinal cord injury (SCI) population, the level of polypharmacy with respect to seven classes of high-risk drugs commonly used to treat secondary conditions in the SCI population, and the overall risks for drug-related problems (DRP) related to polypharmacy. Design: A retrospective case-control design. Setting: A commercially available claims dataset that included patient cases from 4800 hospitals in the USA between 2007 and 2009. Participants: Individuals with tetraplegia, paraplegia, and those with SCI but not specified as either tetraplegia or paraplegia as well as a control population of randomly selected, age-and sex-matched individuals without a diagnosis of SCI. Outcome measures: The overall prevalence of polypharmacy, the prevalence of commonly prescribed high-risk medications, and the prevalence of reported DRPs. Results: Overall, the patients in the SCI population were prescribed significantly more medications than their control counterparts. There was a higher rate of individuals being prescribed medications from multiple highrisk classes (e.g. analgesic-narcotics, anticonvulsant, antidepressant, and skeletal muscle relaxer), as well as multiple medications within each class (e.g. multiple analgesic-narcotics). The SCI group had a higher incidence of DRPs. Conclusion: Our results are some of the first to demonstrate the extent of polypharmacy in individuals with SCI, including commonly prescribed high-risk medications, leading to a higher rate of DPRs. The higher rate of polypharmacy and DRPs can impact rehabilitation goals and community integration following neurologic injury.

We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2–3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2–0.8 Hz) for all injured animals relative to low frequency MAP power (0.02–0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP.

Summary: Two of the most prevalent secondary complications following spinal cord injury (SCI), besides loss of function and/ or sensation below the level of injury, are uncontrolled muscle spasticity and hypertensive autonomic dysreflexia. Despite the desires of the SCI community, there have been few advances in the treatment and/or management of these fundamental impediments to the quality of life associated with chronic SCI. Therefore, the purpose of this review is to focus on current drug treatment strategies that alleviate symptoms of spasticity and autonomic dysfunction. Subsequently, looking ahead, we discuss whether individuals suffering from autonomic dysreflexia and/or muscle spasms can take certain compounds that specifically and rapidly block the neurotransmission of pain into the injured spinal cord to get rapid relief for both aberrant reflexes for which painful stimuli below the level of SCI are common precipitants.

Massage has the potential to attenuate the inflammatory process, facilitate early recovery, and provide pain relief from muscular injuries. In this hypothesis-driven paper, we integrate the concept of mechanotransduction with the application of massage to explore beneficial mechanisms. By altering signaling pathways involved with the inflammatory process, massage may decrease secondary injury, nerve sensitization, and collateral sprouting, resulting in increased recovery from damage and reduction or prevention of pain. Our goal is to provide a framework that describes our current understanding of the mechanisms whereby massage therapy activates potentially beneficial immunomodulatory pathways.