Phenotypic modification of dorsal root ganglion (DRG) neuronsrepresents an important mechanism underlying neuropathic pain. However, the nerve injury-induced molecular changes are not fully identified. To determine the molecular alterations in a broader way, we have carried out cDNA array on the genes mainly made from the cDNA libraries of lumbar DRGs of normal rats and of rats 14 days after peripheral axotomy. Of the 7,523 examined genes and expressed sequence tags (ESTs), the expression of 122 genes and 51 expressed sequence tags is strongly changed. These genes encompass a large number of members of distinct families, including neuropeptides, receptors, ion channels, signal transduction molecules, synaptic vesicle proteins, and others. Of particular interest is the up-regulation of ␥-aminobutyric acidA receptor ␣5 subunit, peripheral benzodiazepine receptor, nicotinic acetylcholine receptor ␣7 subunit, P2Y1 purinoceptor, Na ؉ channel ␤2 subunit, and L-type Ca 2؉ channel ␣2␦-1 subunit. Our findings therefore reveal dynamic and complex changes in molecular diversity among DRG neurons after axotomy. N europathic pain is caused by nervous system lesions, persists long after the initiating event has healed, and may result from a pathological operation of the nervous system. Available therapies are often inadequate. Therefore, it is essential to identify the molecular changes that may lead to neuropathic pain, both for understanding underlying mechanisms and developing new therapies.The peripherally axotomized animal represents one model to study the mechanisms of neuropathic pain (1). After the finding that vasoactive intestinal polypeptide is up-regulated after axotomy (2), many subsequent studies have reported dramatic changes in individual molecules in dorsal root ganglion (DRG) after nerve injury, and some molecules are implicated in generation and maintenance of pain (3-5). For example, downregulation of -opioid receptor and up-regulation of cholecystokinin B receptor (6, 7) may contribute to the attenuated analgesic effect of opioids in neuropathic pain. Up-regulation of adrenoreceptor ␣2A (A-R␣2A) and neuropeptide Y (NPY) Y2-R enhances sympathetically maintained pain (8, 9). The increase in Na ϩ channel (Ch) III mediates ectopic activity in injured neurons (10). Moreover, hyperalgesia appearing during the course of nerve regeneration suggests a correlation between regeneration and pain. Neurotrophins play important roles in both nerve regeneration and regulation of the expression of some neuropeptides and ion channels (11,12). Taken together, current knowledge suggests that changes in gene expression in DRGs may contribute to the generation and development of neuropathic pain. However, although in situ hybridization and other methods have been extensively used to study the changes of individual genes in DRG, a limiting factor with these methods is the lack of a comprehensive overview of the alteration of gene expression. Here, we took a broader approach, a cDNA array (13), to gain a global view of the chang...