Activation of spinal serotonin(2A/2C) receptors augments nociceptive responses in the rat.

The role of spinal 5-HT(2A/2C) receptors in the regulation of spinal nociceptive transmission was studied. The 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the antagonist ketanserin tartrate were administered intrathecally immediately before the formalin test. Activation of spinal 5-HT(2A/2C) receptors increased the pain-like behavioural response in both the early and late phases. The findings support the hypothesis that spinal 5-HT(2A/2C) receptors augment the spinal afferent nociceptive impulses induced by peripheral inflammation.

Differential effects of activation of lumbar and thoracic 5-HT2A/2C receptors on nociception in rats.

The role of 5-HT2 receptors in nociceptive behaviour of rats was investigated using spinal administration of the 5-HT2A/2C receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI), the 5-HT2A/2C antagonist ketanserin and the glutamate receptor agonist NMDA. Nociceptive behaviour was scored after injections at upper thoracic or lumbosacral levels. DOI (0.1-10 mM, 15 microl) administered at the upper thoracic level induced pain-like behaviour in a dose-dependent manner and a long-lasting motor depression at the greatest dose. At the lumbosacral level a similar dose-dependent pain-like behaviour was observed, but it was less pronounced. Motor depression was not observed at any dose. Ketanserin injected before DOI blocked both nociceptive and motor effects. Stimulation of both NMDA and 5-HT2A/2C receptors had a mutually potentiating effect. The present results show that the effects of DOI were more pronounced at the upper thoracic than at the lumbosacral level. This is possibly caused by the difference in 5-HT2A/2C receptor density at the two levels. The motor depression induced by the greatest dose of DOI given at the upper thoracic level appears to mask the pain-like behaviour. The nociceptive behaviour seen after DOI injection is further increased following co-injection of NMDA.

Lumbar catheterization of the spinal subarachnoid space in the rat.

The method commonly used for catheterization of the lumbar subarachnoid space in the rat implies inserting the catheter through the atlanto-occipital (A-O) membrane and moving the catheter caudally along the spinal cord. The method is associated with a considerable morbidity. A method for direct catheterization of the lumbar subarachnoid space was therefore developed. Major surgery was avoided by using a catheter-through-needle technique. Of 32 rats, none died. There were no signs of neurological disturbances, and all animals gained weight as normal the first week after implantation. Data from rats catheterized by the A-O method were used for comparison. Of 40 animals, 2 died, 11 showed signs of neurological disturbances, and the mean weight was reduced during the first week after catheterization. The two groups of animals showed different behavioural responses to intrathecal injection of N-methyl-D-aspartate (NMDA, 0.1-1.6 mM, 15 microliters) which is thought to stimulate afferent pathways mediating nociception. Animals with a lumbar catheter showed licking, biting and scratching behaviour in a dose-related manner for concentrations up to 1.6 mM. The animals with A-O catheters showed a maximum level of this behaviour already at 0.4 mM, while 0.5 mM induced convulsions. A possible explanation of this difference in response to NMDA could be a long-lasting pain state in the A-O group, caused by catheter-induced changes in the spinal cord and by the extensive surgery. It is concluded that the direct lumbar catheterization has several advantages compared to the A-O method, decreasing the suffering of the animals, the neurological disturbances and the interference with nociceptive functions of the spinal cord.