Sarah M. Abshire

Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection

Complete thoracic (T) spinal cord injury (SCI) above the T6 level typically results in autonomic dysreflexia, an abnormal hypertensive condition commonly triggered by nociceptive stimuli below the level of SCI. Overexpression of nerve growth factor in the lumbosacral spinal cord induces profuse sprouting of nociceptive pelvic visceral afferent fibers that correlates with increased hypertension in response to noxious colorectal distension. After complete T4 SCI, we evaluated the plasticity of propriospinal neurons conveying visceral input rostrally to thoracic sympathetic preganglionic neurons. The anterograde tracer biotinylated dextran amine (BDA) was injected into the lumbosacral dorsal gray commissure (DGC) of injured/nontransected rats immediately after injury (acute) or 2 weeks later (delayed). At 1 or 2 weeks after delayed or acute injections, respectively, a higher density (P < 0.05) of BDA+ fibers was found in thoracic dorsal gray matter of injured vs. nontransected spinal cords. For corroboration, fast blue (FB) or cholera toxin subunit beta (CTb) was injected into the T9 dorsal horns 2 weeks postinjury/nontransection. After 1 week transport, more retrogradely labeled (P < 0.05) DGC propriospinal neurons (T13–S1) were quantified in injured vs. nontransected cords. We also monitored immediate early gene c‐fos expression following colorectal distension and found increased (P < 0.01) c‐Fos+ cell numbers throughout the DGC after injury. Collectively, these results imply that, in conjunction with local primary afferent fiber plasticity, injury‐induced sprouting of DGC neurons may be a key constituent in relaying visceral sensory input to sympathetic preganglionic neurons that elicit autonomic dysreflexia after high thoracic SCI. J. Comp. Neurol. 509:382–399, 2008.

Tumor necrosis factor-alpha (TNF-α) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes

BackgroundWe have shown functional expression of several TRP channels on human synovial cells, proposing significance in known calcium dependent proliferative and secretory responses in joint inflammation. The present study further characterizes synoviocyte TRP expression and activation responses to thermal and osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis factor alpha (TNF-α, EC50 1.3221 × 10-10g/L).ResultsFluorescent imaging of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic calcium oscillations elicited by (1) TRPV1 agonists capsaicin and resiniferatoxin (20 – 40% of cells), (2) moderate and noxious temperature change, and (3) osmotic stress TRPV4 activation (11.5% of cells). TNF-alpha pre-treatment (1 ng/ml, 8 – 16 hr) significantly increases (doubles) capsaicin responsive cell numbers and [Ca2+]i spike frequency, as well as enhances average amplitude of temperature induced [Ca2+]i responses. With TNF-alpha pre-treatment for 8, 12, and 16 hr, activation with 36 or 45 degree bath solution induces bimodal [Ca2+]i increase (temperature controlled chamber). Initial temperature induced rapid transient spikes and subsequent slower rise reflect TRPV1 and TRPV4 channel activation, respectively. Only after prolonged TNF-alpha exposure (12 and 16 hr) is recruitment of synoviocytes observed with sensitized TRPV4 responses to hypoosmolarity (3–4 fold increase). TNF-alpha increases TRPV1 (8 hr peak) and TRPV4 (12 hr peak) immunostaining, mRNA and protein expression, with a TRPV1 shift to membrane fractions.ConclusionTNF-α provides differentially enhanced synoviocyte TRPV1 and TRPV4 expression and [Ca2+]i response dependent on the TRP stimulus and time after exposure. Augmented relevance of TRPV1 and TRPV4 as inflammatory conditions persist would provide calcium mediated cell signaling required for pathophysiological responses of synoviocytes in inflammatory pain states.

Massage timing affects postexercise muscle recovery and inflammation in a rabbit model.

PURPOSE This study compared the effect of immediate versus delayed massage-like compressive loading (MLL) on peak isometric torque recovery and inflammatory cell infiltration after eccentric exercise (EEX). METHODS Eighteen skeletally mature New Zealand White rabbits were instrumented with peroneal nerve cuffs for the stimulation of hindlimb tibialis anterior muscles. After a bout of EEX, rabbits were randomly assigned to an MLL protocol (0.5 Hz, 10 N, 15 min) that started immediately post-EEX, 48 h post-EXX, or no-MLL control and performed for four consecutive days. A torque-angle (T-Θ) relationship was obtained for 21 joint angles pre- and post-EEX and after four consecutive days of MLL or no-MLL. Muscle wet weights and immunohistochemical sections were obtained after final treatments. RESULTS EEX produced an average 51% ± 13% decrease in peak isometric torque output. The greatest peak torque recovery occurred with the immediate application of MLL. There were differences in torque recovery between immediate and delayed MLL (P = 0.0012), immediate MLL and control (P < 0.0001), and delayed MLL and control (P = 0.025). Immunohistochemical analysis showed 39.3% and 366.0% differences in the number of RPN3/57 and CD11b-positive cells between immediate (P = 0.71) and delayed MLL (P = 0.12). The area under the T-Θ curve showed a difference for immediate (P < 0.0001) and delayed (P = 0.0051) MLL as compared with control. Exercise produced an average 10° ± 0.2° rightward shift from preexercise peak isometric torque angle. Control, immediate MLL, and delayed MLL produced an average leftward angular shift from the postexercise angle (P = 0.28, P = 0.03, and P = 0.47, respectively). CONCLUSION Post-EEX, immediate MLL was more beneficial than delayed MLL in restoring muscle function and in modulating inflammatory cell infiltration. These findings invite similar human studies to make definitive conclusions on optimal timing of massage-based therapies.

Enhanced skeletal muscle regrowth and remodelling in massaged and contralateral non‐massaged hind limb

Muscle fibre cross sectional area is enhanced with massage in the form of cyclic compressive loading during regrowth after atrophy. Massage enhances protein synthesis of the myofibrillar and cytosolic, but not the mitochondrial fraction, in muscle during regrowth. Focal adhesion kinase activation and satellite cell number are elevated in muscles undergoing massage during regrowth. Muscle fibre cross sectional area and protein synthesis of the myofibrillar fraction, but not DNA synthesis, are elevated in muscle of the contralateral non‐massaged limb. Massage in the form of cyclic compressive loading is a potential anabolic intervention during muscle regrowth after atrophy.