May 23, 2012 A new study finds that transplanting embryonic cells into adult mouse spinal cord can alleviate persistent pain. The research, published by Cell Press in the May 24th issue of the journal Neuron, suggests that reduced pain results from successful integration of the embryonic cells into the host spinal cord. The findings open avenues for clinical strategies aimed not just at treating the symptoms of chronic debilitating pain, but correcting the underlying disease pathology.
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. Neuropathic pain is thought to involve the loss of inhibitory neurons that release the chemical GABA, which is an inhibitory neurotransmitter that controls the excitability of neurons, including neurons that transmit pain information.
"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," explains senior study author, Dr. Allan Basbaum from the University of California, San Francisco. "Therefore, new therapeutic approaches for neuropathic pain are essential." Dr. Basbaum and colleagues explored whether replacement of the damaged inhibitory neurons might be useful for reducing neuropathic pain.
The researchers 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," concludes 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."
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- João M. Bráz, Reza Sharif-Naeini, Daniel Vogt, Arnold Kriegstein, Arturo Alvarez-Buylla, John L. Rubenstein, Allan I. Basbaum. Forebrain GABAergic Neuron Precursors Integrate into Adult Spinal Cord and Reduce Injury-Induced Neuropathic Pain. Neuron, 2012; 74 (4): 663 DOI: 10.1016/j.neuron.2012.02.033
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