Searching for Genes Responsibile for Neuropathic Pain

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DESCRIPTION (provided by applicant): Neuropathic pain resulting from peripheral nerve injury represents an important component of various dental and orofacial disorders affecting the quality of life of dental patients. The molecular mechanisms of neuropathic pain disorders are not well understood. Pharmacological and physiological studies have suggested that altered production offimctional proteins, or expression of genes, in sensory neurons plays an important role in abnormal sensory processing after nerve injury. Thus, characterizing these changes after nerve injury is a critical step toward our better understanding of neuropathic pain and development of specific therapeutic agents or strategies for neuropathic pain treatment. However, tools for studying gene expression at the protein level are limited by their specificity and availability. Since mRNAs are blueprints of encoded proteins and gene chip technology is available for large scale identification of altered gene expression at the mRNA level, we propose to use this new technique to identify genes whose altered expression in sensory neurons following nerve injury correlates with neuropathic pain development. Gone chip analyses will be used to identify genes with altered expression in lumbar dorsal root ganglia (DRG, containing sensory neurons) from nerve-injured rats compared to that in sham-operated rats using a well defined rat neuropathic pain model: tight ligation of L5/L6 lumbar spinal nerves. To distinguish potential target genes linked to neuropathic pain from those linked to nerve injury only, gene expression patterns in DRG will be compared between nerve injured Harlan and Holzman rats, different species either susceptible or resistant to neuropathic pain development, respectively; and between nerve injured Harlan rats either with neuropathic pain or fully recovered from neuropathic pain. Preliminary validations of altered target gene expression in nerve injured rats will be performed with RNase protection, Western blot analyses and in situ hybridization.