α-Conotoxin RgIA protects against the development of nerve injury-induced chronic pain and prevents both neuronal and glial derangement

Neuropathic pain affects millions of people worldwide, causing substantial disability and greatly impairing quality of life. Commonly used analgesics or antihyperalgesic compounds are generally characterized by limited therapeutic outcomes. Thus, there is a compelling need for novel therapeutic strategies able to prevent nervous tissue alterations responsible for chronic pain. The alpha 9 alpha 10 nicotinic acetylcholine receptor antagonist alpha-conotoxin RgIA (RgIA), a peptide isolated from the venom of a carnivorous cone snail, induces relief in both acute and chronic pain models. To evaluate potential disease-modifying effects of RgIA, the compound was given to rats following chronic constriction injury (CCI) of the sciatic nerve. Two or 10 nmol RgIA injected intramuscularly once a day for 14 days reduced the painful response to suprathreshold stimulation, increased pain threshold to nonnoxious stimuli, and normalized alterations in hind limb weight bearing. Histological analysis of the sciatic nerve revealed that RgIA prevented CCI-induced decreases of axonal compactness and diameter, loss of myelin sheath, and decreases in the fiber number. Moreover, RgIA significantly reduced edema and inflammatory infiltrate, including a decrease of CD86(+) macrophages. In L4-L5 dorsal root ganglia, RgIA prevented morphometric changes and reduced the inflammatory infiltrate consistent with a disease-modifying effect. In the dorsal horn of the spinal cord, RgIA prevented CCI-induced activation of microglia and astrocytes. These data suggest that RgIA-like compounds may represent a novel class of therapeutics for neuropathic pain that protects peripheral nervous tissues as well as prevents central maladaptive plasticity by inhibiting glial cell activation. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.