Methods of reducing or abolishing neuropathic pain in humans and animals are discussed. In some examples administration of the apoptosis inhibitor tauroursodeoxycholic acid (TUDCA), greatly reduced both neuronal loss and the increase in glia, and partially reversed spinal nerve ligation (SNL)-induced mechanical hypersensitivity. Among RVM neurons, serotonergic (5-HT) neurons decreased by 35% ipsilateral to SNL. In some examples, the density of 5-HT immunoreactive varicosities in the superficial dorsal horn of the spinal cord was lower ipsilateral to SNL. The RVM 5-HT neurons that remained after SNL appeared to facilitate nociception. When rats that had undergone SNL were treated with the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), mechanical withdrawal thresholds increased significantly. In some examples nerve injury induces death of antinociceptive RVM neurons which can be reduced or abolished by TUDCA. In some examples, that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.
