Transmission of Chronic Nociception by Spinal Neurons Expressing the Substance P Receptor.

Transmission of Chronic Nociception by Spinal Neurons Expressing the Substance P Receptor

Nichols ML, Allen BJ, Rogers SD, et al (Departments of Preventative Sciences, Psychiatry, and Neuroscience, and Cancer Center, University of Minnesota, Minneapolis, Minn; Molecular Neurobiology Lab (151), Veteran Affairs Medical Center, Minneapolis, Minn; Advanced Targeting Systems, San Diego, Calif), Science. 1999;286:1558-1561.

According to the authors, some researchers have said that tissue damage or ongoing disease states, which result in sensitization of primary afferent and spinal cord neurons, cause chronic pain. The authors of this article stated that increased sensitivity to both noxious (hyperalgesia) and non-noxious (allodynia) stimuli was difficult to manage with present-day pharmacological and surgical approaches.

A complex study of pain reduction was conducted from observations of animal behavior, and immunoreactive cell and immunofluorescence techniques were used. Pain-inducing stimuli--capsaicin, formalin, carrageenan, and ligation of the L5 and L6 spinal nerves--were used in various schedules to observe the rate, length, and character of paw-flinching behaviors in rats. Control animals were treated with saline. A selective cytotoxin, substance P-saporin (SP-SAP), was intrathecally infused in the spinal cord of rats in various concentrations. The authors noted that the spinal neurons were ablated with the cytotoxin. Laboratory techniques were discussed, and the concentration-response relations for SP-SAP were determined and charted.

According to the authors, the substance P receptor (SPR)-expressing spinal neurons represent less than 5% of the total neurons in the dorsal horn, and the majority of spinothalamic and spinoparabrachial neurons in lamina I of the dorsal horn express SPR. Spinoparabrachial and spinothalamic neurons function in the ascending transmission of impulses of acute noxious stimuli, and SPR activation in spinothalamic neurons may be involved in the development of hyperalgesia according to a study cited in the article.

The authors found that the major site of morphine action was not SPR-expressing neurons in the dorsal horn. According to the authors, SP-SAP treatment had long-term efficacy and no apparent side effects, which appeared to be related to the restricted nature and specificity of SP-SAP action. They pointed out that neuropathic and inflammatory pain arise from different mechanisms.

The investigators found that opiates remain a viable pain therapy after SP-SAP treatment. Loss of the SPR-expressing spinal neurons resulted in decreased thermal hyperalgesia and mechanical allodynia, which are associated with chronic neuropathic and inflammatory pain states. Therefore, they stated that these SPR-expressing neurons play a pivotal role in the generation as well as maintenance of chronic pain.

The authors debated whether the same SPR-expressing neurons or different subsets of them convey the experience of chronic neuropathic and inflammatory pain; the evidence suggested that a uniting feature of many spinal and forebrain neurons that express SPR was their involvement in a response to tissue injury and stress. The authors stated that a study of gene and protein changes in spinal neurons during nociception would provide valuable data and insight into the mechanisms of chronic pain.

Sandra L Jones, PT North Hollywood, Calif