Stephen B. McMahon

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The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating(More)
Homologous recombination was utilized to generate mice with a deletion in the coding sequence of the nerve growth factor (NGF) gene. Animals homozygous for NGF disruption failed to respond to noxious mechanical stimuli, and histological analysis revealed profound cell loss in both sensory and sympathetic ganglia. Within dorsal root ganglia, effects of the(More)
Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal(More)
The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide(More)
We have studied the distribution and regulation of the P2X3 receptor (a ligand-gated ion channel activated by ATP) in adult dorsal root ganglion (DRG) neurons using a polyclonal antibody. P2X3 receptor immunoreactivity was normally present in about 35% of L4/5 DRG neurons, virtually all small in diameter. In the dorsal horn, P2X3 receptor expression was(More)
Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting(More)
Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme(More)
Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC(More)
Immunocytochemistry has been used to examine the location of trkA, the high-affinity receptor for nerve growth factor, in adult rat dorsal root ganglia, trigeminal ganglia and spinal cord. TrkA immunoreactivity was observed in small and medium sized ganglion cells and in the dorsal horn of the spinal cord. In lumbar L4 and L5 ganglia trkA-immunoreactive(More)