This manuscript is intended to give a basic review of the peripheral and spinal neuronal mechanisms involved in the processing of musculoskeletal pain. There is a complicated neuronal network in the periphery and the spinal cord for the processing of nociceptive information. Injury to a muscle (inflammation or ischemia) or a joint (inflammation) results in sensitization of peripheral nociceptors. There is then an increased transmission to and increased release of neurotransmitters in the dorsal horn of the spinal cord. Dorsal horn neurons sensitized by the peripheral injury demonstrate increased background activity, increased receptive field size, and increased responses to peripherally applied stimuli. The increased release of neurotransmitters and the sensitization of dorsal horn neurons is dependent on activation of N-methyl-D-aspartate (NMDA), non-NMDA excitatory amino acid, and neurokinin 1 receptors. Behavioral changes typical of inflammatory pain are observed in arthritic rats. These behavioral changes can be modified by a variety of drugs, including opioids, excitatory amino acid receptor antagonists, or neurokinin receptor antagonists. In addition to processing nociceptive information following joint or muscle injury, the spinal cord controls peripheral joint inflammation. Production of dorsal root reflexes, antidromic action potentials, would be expected to result in the release of inflammatory neuropeptides [substance P and calcitonin gene-related peptide (CGRP)] from the terminals of primary afferents at the site of injury. The release of substance P and CGRP would potentiate the inflammatory response in the periphery.