Allodynia is pain that results from a normally innocuous stimulus. Allodynia in human patients is a distressing condition that commonly occurs in neuropathic pain states and in inflammation. Several proposals have been made concerning mechanisms that underlie allodynia. We hypothesize that a plastic change in nociceptive dorsal horn neurons called central sensitization is responsible for the development of mechanical allodynia. Our laboratory has examined the possible role of central sensitization of dorsal horn nociceptive neurones, including spinothalamic tract cells, in mechanical allodynia. Our experimental models were peripheral neuropathy following tight ligation of one or more spinal nerves (Chung model) and intradermal injection of capsaicin. Spinal nerve ligations were done under sodium pentobarbital anaesthesia. Capsaicin injections were made under halothane or pentobarbital anaesthesia. Most experiments have been done in rats, but some, particularly those in which electrophysiological recordings were made from spinothalamic tract neurones, were done in monkeys (Macaca fascicularis). These animals were anaesthetized initially with halothane and nitrous oxide, and then anaesthesia was maintained with a mixture of α-chloralose and sodium pentobarbital. At the end of the experiments, the animals were humanely killed. Wide dynamic range dorsal horn neurones normally respond weakly to tactile stimuli and maximally to noxious stimuli. After peripheral nerve injury or acute inflammation, such as following an intradermal injection of capsaicin, these neurones could respond as strongly to tactile stimuli as they previously had to noxious mechanical stimuli. If thalamo-cortical neurones reflect these changed responses, the resulting sensation may be interpreted as pain rather than as touch. This could account for mechanical allodynia. We attribute the enhanced tactile responses of nociceptive dorsal horn neurones to central sensitization. We have evidence from pharmacological experiments that this process is initiated by synaptic release of glutamate and peptides, including substance P and calcitonin gene-related peptide, from the terminals of nociceptors in the dorsal horn. Actions at NMDA, NK1, CGRP1 and other receptors result in the activation of several signal transduction pathways (including the CaMKII, PKC, PKA, and NO/PKG cascades), which in turn cause the phosphorylation of proteins, such as the NR1 subunits of NMDA receptors and GluR1 subunits of AMPA receptors. Based on the work of others, we presume that phosphorylated glutamate receptors become more responsive to glutamate and more receptors may be inserted into the surface membrane. These changes then increase the responses of wide dynamic range nociceptive neurones to glutamate released from tactile afferents. Simultaneously, the responses of inhibitory amino acid receptors to GABA and glycine are reduced. We speculate that it is possible that phosphorylated inhibitory amino acid receptors become desensitized, reducing the amount of inhibition of dorsal horn neurones. We have found that the duration of these changes is regulated by protein phosphatase activity.