Table 5.

Mechanisms of action of controlled physical exercise on nerve repair and regeneration.

Kind of Exercise	Action of Exercise on Nerve Repair	In-Depth Features	References
Modulator of the Neurotrophins
Physical exercise	Increment of neurotrophin levels	For regenerating neurons	[7,14,34,79]
	Increment of neurotrophin levels such as BDNF	For the survival and regeneration of injured axons	[7,14,39]
	Induction of GMF and BDNF	GMF could be necessary for exercise induction of BDNF and could promote neuroprotection through BDNF production	[18]
High-intensity physical exercise	Reduction both in early hyperalgesia, decreasing the production of NGF in the skin and in sensory neurons, and late hyperalgesia related to reinnervation by regenerating nerve fibers	Early hyperalgesia is associated with collateral sprouting of intact nerve fibers	[79]
High-intensity physical exercise	Reduction in BDNF at the level of microglia and dorsal root ganglia	Modulation of neurotrophin mechanisms that regulate growth and excitability of sensory neurons after peripheral nerve injury	[53]
Treadmill running	Hyperalgesic responses are strongly dependent on NGF	The early reduction in hyperalgesia is likely associated with the reduction in local NGF production	[79]
Low intensity, but not high intensity	Low-intensity, but not high-intensity treadmill increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation	Treadmill elevated levels of GAP-43 mRNA and protein, and hosphor-ERK1/2 protein in the injured sciatic nerves	[21]
Voluntary exercise	Increase in axonal regeneration through a neurotrophin-dependent mechanism and neurite outgrowth	Increase in expression of several molecules associated with the action of BDNF on synaptic function	[13,65,80]
Voluntary exercise	Sensory ganglia from the 3- and 7-day-exercised animals contained higher brain-derived neurotrophic factor, neurotrophin 3, synapsin I, and GAP43 mRNA levels than those from sedentary animals	Increase in axonal regeneration after 3–7 days of exercises through a neurotrophin-dependent mechanism	[7]
Voluntary exercise	Modulation of neurotrophin signal	Regulating the growth of sensory neurons	[7]
Regular eccentric exercise	Reduction in TNF-α in the muscle and increase in IGF-1 in nerve. Activation of serotoninergic and noradrenergic systems (descending pain inhibitory systems) improved morphological nerve regeneration	In sciatic nerve crush-subjected animals: reduced mechanical and cold hyperalgesia accelerated motor functional recovery	[57]
Electrical stimulation and exercises	Increase in BDNF and trkB expression	Increase in the expression of BDNF and trkB mRNA in regenerating femoral motoneurons	[10]
Brief electrical stimulation	Decrease in dorsal root ganglion neurons regenerating into cutaneous and muscle branches, increase in numbers of neurons that regenerated axons, and the expression of GAP-43 mRNA in the regenerating neurons and of BDNF	-	[16]
Electrical stimulation	Up-regulation of S-100, BDNF, Par-3	-	[17]
Swimming exercises	Increase nerve repair-associated makers, and calcitonin gene-related peptide (CGRP)	-	[19]
Sprouting
High intensity	Inhibition of denervation and induction of early collateral sprouting	Hampering of longer duration nerve regeneration	[79]
Increase in axonal outgrowth
Prolonged treadmill exercise	Promotion of enlargement of fast-fatigable and fast–intermediate motor units	At the level of partially denervated gastrocnemius	[37]
Electrical stimulation	FES-induced acceleration of axon regeneration in post-surgical carpal tunnel syndrome	Improved MUNE, motor units, terminal motor latency, sensory nerve conduction values	[72]
Regulation of neuronal cotransporters
High-intensity exercises	Prevention of NKCC1/KCC2 deregulation	It is a nerve injury-dependent mechanism of central disinhibition	[53]

Growth-Associated Protein 43, GAP-43; Brain-Derived Neurotrophic Factor, BDNF; Nerve Growth Factor, NGF; Na-K-2Cl Cotransporter isoform 1, NKCC1; K-Cl Cotransporter isoform 2, KCC2; Motor unit number estimation, MUNE.