The findings suggest avenues for clinical strategies aimed at correcting the underlying disease pathology as opposed to treating the symptoms of chronic debilitating pain.
"Pharmacological approaches to managing neuropathic pain enhance GABA-mediated inhibition. However, some patients do not respond to these therapies and there are significant adverse side effects," said Dr. Allan Basbaum from the University of California, San Francisco.
There are two major classes of chronic pain: inflammatory pain that results from injury to tissue, such as muscle and bone, and neuropathic pain from injury to nerves, for example, in the limbs or face. Damage to nerves can occur after physical trauma and from chemotherapy drugs. With neuropathic pain, the pain occurs in the absence of stimulation, and there is hypersensitivity and exacerbated pain to stimuli that would not normally cause pain.
Basbaum's team transplanted immature GABA neurons from mouse fetal brain into the spinal cord of mice with nerve injury-induced pain, a model for human neuropathic pain. The transplanted cells not only survived, but made connections with appropriate targets and integrated into the host spinal cord circuitry. This resulted in an almost complete reversal of the mechanical hypersensitivity generated in a nerve injury model of neuropathic pain. In contrast, the transplant procedure was not effective at reducing pain in a mouse model of inflammatory pain, which is induced by tissue injury.
Taken together, the findings have exciting implications for a cell-based treatment of neuropathic pain in humans. "Our strategy not only ameliorates the symptoms of neuropathic pain but, importantly, is also potentially disease modifying," said Dr. Basbaum. "It is worth considering whether transplants such as these might have clinical utility in humans, a great advantage being that the adverse side effects associated with drug administration can be avoided."
Adapted from the University of California San Francisco announcement.
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