Investigation of primate primary somatosensory cortex neuronal responses to persistent noxious input produced by inflammation

Few studies exist which explore the processing of persistent noxious input associated with inflammation. In a primate model, joint inflammation has been shown to sensitize spinothalamic tract neurons. Only in a rat model have the effects of persistent painful input been characterized at supra-spinal levels. Thus, the specific aims were to: (1) investigate whether hyperalgesia is present during persistent inflammation in non-human primates, (2) explore how persistent nociceptive input affects properties of non-nociceptive and nociceptive neurons in primate primary somatosensory cortex (SI), (3) explore the relationship between nociceptive-induced hyperexcitability and NMDA receptor activity in SI, and (4) compare and contrast observations made using persistent and transient noxious stimuli models in primate SI.; To examine hyperalgesia, a monkey was trained to detect small thermal shifts in both the innocuous and the noxious range. The speed with which the animal detected each shift and his accuracy at detecting the shift was measured. Twenty-four hours after carrageenan (30 mg, subcutaneously) induced inflammation, shifts from noxious temperatures were detected more quickly without a change in accuracy. The increased detection speed gradually returned to normal over the next two days in a timecourse consistent with the observed inflammation. This behaviorally demonstrates hyperalgesia in this monkey.; Neurons isolated 24 hours after inflammation compared to a control population showed no major differences in the relative proportions of nociceptive and non-nociceptive neurons, evoked neural responses to mechanical stimuli, or background activity. There was a trend for an increase in receptive field size of nociceptive neurons after inflammation, but it was not statistically significant. However, the receptive field size of cells responding exclusively to non-noxious stimulation was significantly smaller than in the control population. Systemic injection of MK-801, an NMDA receptor antagonist (0.1 mg/kg), after inflammation depressed the evoked responses to noxious stimulation, but background activity and all other evoked responses were unchanged.; By comparison, the changes in cortical processing after transient noxious stimulation, intradermal capsaicin injection (200 {dollar}mu{dollar}g), were pronounced. There was significant receptive field expansion, and increased background activity was detectable within five minutes. The evoked responses to mechanical stimuli were also increased. Injecting MK-801 attenuated the receptive field expansion, so the NMDA receptor is linked to the process. Experiments comparing the systemic effect of MK-801 with the intrathecal effect of MK-801 (10 {dollar}mu{dollar}g) on cortical neurons provided evidence that the changes seen at the cortical level cannot be totally accounted for by changes at the spinal level.; In spite of having a strong role in processing transient noxious stimuli, the cortex appears not to be critically involved in the processing of persistent painful input such as that caused by carrageenan injection. These data do not support the assertion that this region is essential to the experience of persistent pain.