The nitric oxide dependence of cutaneous microvascular function to independent and combined hypoxic cold exposure

When separated from local cooling, whole body cooling elicited cutaneous reflex vasoconstriction via mechanisms independent of nitric oxide removal. Hypoxia elicited cutaneous vasodilatation via mechanisms mediated primarily by nitric oxide synthase, rather than xanthine oxidase-mediated nitrite reduction. Cold-induced vasoconstriction was blunted by the opposing effect of hypoxic vasodilatation, whereas the underpinning mechanisms did not interrelate in the absence of local cooling. Full vasoconstriction was restored with nitric oxide synthase inhibition.

Repeated and patterned stimulation of cutaneous reflex pathways amplifies spinal cord excitability

Priming via patterned stimulation of the nervous system induces neuroplasticity. Yet, accessing previously known cutaneous reflex pathways to alter muscle reflex excitability has not yet been examined. Here, we show that sensory stimulation of the cutaneous afferents that innervate the foot sole can amplify spinal cord excitability, which, in this case, is attributed to reductions in presynaptic inhibition.

Cutaneous inputs from perineal region facilitates and modulates spinal locomotor activity and reduces cutaneous reflexes from the foot in spinal cats

It is well known that mechanically stimulating the perineal region potently facilitates hindlimb locomotion and weight support in mammals with a spinal transection (spinal mammals). However, how perineal stimulation mediates this excitatory effect is poorly understood. We evaluated the effect of mechanically stimulating (vibration or pinch) the perineal region on ipsilateral (9-14 ms onset) and contralateral (14-18 ms onset) short-latency cutaneous reflex responses evoked by electrically stimulating the superficial peroneal or distal tibial nerve in seven adult spinal cats where hindlimb movement was restrained. Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the perineal region. We found that vibration or pinch of the perineal region effectively triggered rhythmic activity, unilateral and bilateral to nerve stimulation. When electrically stimulating nerves, adding perineal stimulation modulated rhythmic activity by decreasing cycle and burst durations and by increasing the amplitude of flexors and extensors. Perineal stimulation also disrupted the timing of the ipsilateral rhythm, which had been entrained by nerve stimulation. Mechanically stimulating the perineal region decreased ipsilateral and contralateral short-latency reflex responses evoked by cutaneous inputs, a phenomenon we observed in muscles crossing different joints and located in different limbs. The results suggest that the excitatory effect of perineal stimulation on locomotion and weight support is not mediated by increasing cutaneous reflex gain and instead points to an excitation of central pattern-generating circuitry. Our results are consistent with a state-dependent modulation of reflexes by spinal interneuronal circuits.Significance StatementMechanically stimulating the skin of the perineal region strongly facilitates hindlimb locomotion in mammals following a complete spinal cord injury (SCI). Despite its remarkable effectiveness in promoting hindlimb locomotion in spinal cord-injured mammals, we do not know how this is mediated. The present study provides data on how inputs from the perineal region interact with neuronal circuits that generate locomotor-like activity and reflexes from the foot. A better understanding of how inputs from the perineal region interact with neuronal circuits of the spinal cord could lead to non-invasive approaches to restore walking in people with SCI.

Mechanically stimulating the lumbar region inhibits locomotor-like activity and increases the gain of cutaneous reflexes from the paws in spinal cats

Mechanically stimulating the dorsal lumbar region inhibits locomotion and reduces weight support during standing in rabbits and cats. However, how this inhibitory effect from the lumbar skin is mediated is poorly understood. Here we evaluated the effect of mechanically stimulating (vibration or pinch) the dorsal lumbar region on short-latency (8- to 13-ms onset) cutaneous reflex responses, evoked by electrically stimulating the superficial peroneal or distal tibial nerves, in seven adult cats with a low thoracic spinal transection (spinal cats). Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the dorsal lumbar region. We found that mechanically stimulating the lumbar region by vibration or manual pinch abolished alternating bursts of activity between flexors and extensors initiated by nerve stimulation. The activity of extensor muscles was abolished bilaterally, whereas the activity of some ipsilateral flexor muscles was sustained during vibration/pinch. Mechanically stimulating the lumbar region increased ipsilateral and contralateral short-latency excitatory responses evoked by cutaneous inputs, a phenomenon that was generalized to muscles crossing different joints and located in different limbs. Our results indicate that the inhibitory effect on locomotion and weight support is not mediated by reducing cutaneous reflex gain and instead points to an inhibition of central pattern-generating circuitry, particularly the extensor component. The results provide greater insight into interactions between different types of somatosensory inputs within spinal motor circuits. NEW & NOTEWORTHY Vibration or pinch of the lumbar region in spinal-transected cats abolished alternating bursts of activity between flexors and extensors initiated by nerve stimulation. Mechanically stimulating the lumbar region increased ipsilateral and contralateral short-latency excitatory responses evoked by cutaneous inputs in hindlimb muscles. Sensory inputs from mechanoreceptors of the lumbar region do not mediate their inhibitory effect on locomotion and weight support by reducing the gain of short-latency excitatory cutaneous reflexes from the foot.

Sensory enhancement amplifies interlimb cutaneous reflexes in wrist extensor muscles

Interlimb neural connections support motor tasks such as locomotion and cross-education strength training. Somatosensory pathways that can be assessed with cutaneous reflex paradigms assist in subserving these connections. Many studies show that stimulation of cutaneous nerves elicits reflexes in muscles widespread across the body and induces neural plasticity after training. Sensory enhancement, such as long-duration trains of transcutaneous stimulation, facilitates performance during rehabilitation training or fatiguing motor tasks. Performance improvements due to sensory stimulation may be caused by altered spinal and corticospinal excitability. However, how enhanced sensory input regulates the excitability of interlimb cutaneous reflex pathways has not been studied. Our purpose was to investigate the effects of sensory enhancement on interlimb cutaneous reflexes in wrist extensor muscles. Stimulation to provide sensory enhancement (2-s trains at 150 Hz to median or superficial radial nerves) or evoke cutaneous reflexes (15-ms trains at 300 Hz to superficial radial nerve) was applied in different arms while participants ( n = 13) performed graded isometric wrist extension. Wrist extensor electromyography and cutaneous reflexes were measured bilaterally. We found amplified inhibitory reflexes in the arm receiving superficial radial and median nerve sensory enhancement with net reflex amplitudes decreased by 709.5% and 695.3% repetitively. This suggests sensory input alters neuronal excitabilities in the interlimb cutaneous pathways. These findings have potential application in facilitating motor function recovery through alterations in spinal cord excitability enhancing sensory input during targeted rehabilitation and sports training. NEW & NOTEWORTHY We show that sensory enhancement increases excitability in interlimb cutaneous pathways and that these effects are not influenced by descending motor drive on the contralateral side. These findings confirm the role of sensory input and cutaneous pathways in regulating interlimb movements. In targeted motor function training or rehabilitation, sensory enhancement may be applied to facilitate outcomes.