| Our previous studies suggest that the pelvic primary afferents project to the intermediolateral nucleus (IML) and dorsal commissural nucleus (DCN) of the lumbosacral spinal cord. The neurons projecting to the lateral parabrachial nucleus (LPB) form an elongated spindle-shaped column extending throughout the IML of the sacral segments. As the collection of pelvic primary afferent terminals and second order neurons the DCN and IML play important roles in the transmission and regulation of the sensory signals, especially the nociception from the pelvic organs.It's been reported that tissue inflammation increases the sensitivity of the colon to mechanical stimuli, which is responsible for the enhanced responses to colorectal distension (CRD). This enhancement involves the activation of spinal NMDA as well as non-NMDA receptors, but not metabotropic receptors.Substance P (SP) acts as an important neuropeptide in the nociceptive pathways. After release from the nerve endings SP binds preferentially to the substance P receptor (SPR) and exerts its physiological effects. Morphological studies show that SP and SPR are abundant in the laminae â… ,â…¢,â…© andmoderately distribute in IML of the spinal cord. After binding to SPR, a kind of G-protein-coupled receptors (GPCRs), SP can induce the hydrolyze of the membrane-bound phosphatidylinositol biphosphate and the elevation of the intracellular level of cyclic adenosine monophosphate (cAMP). And SPR itself internalizes into the cytoplasm. Internalization induced by agonist is a common feature of GPCRs. It's responsible for the desensitization and resensitization of the receptors and the inactivation of the agonists. Internalization of SPR is a reliable indicator of its activation by endogenous neurokinins.Therefore, in the present study, an attempt was made to observe the pain promoting effect of instillation of 5% formalin into the rat colon and the changes of spinal SPR during these processes by using behavioral observation and immunofluorescence histochemistry. Behavioral studies showed that (1) after formalin instillation several behaviors, previously reported to reflect visceral pain, were observed:(Dlower abdominal licking and nibbling;(2)body stretching; â‘¢contraction of the flanks; â‘£whole body contraction. Using the set-up formula we got the pain score (PS). It showed a biphasic feature, that the first phase was within the first 30 min and the second phase was from 75 to 105 min after formalin instillation. (2)SPR antagonist L732138 reduced the first phase nociceptive responses at the dose tested when it was administered 10 min before noxious stimulation. However it had little effect on the second phase. Morphological studies showed that SPR-containing endosomes began to migrate to the interior of the neurons at 8 min after formalin instillation. At 15 min 65.8% SPR-immunoreactive (SPR-ir) neurons of the IML and DCN had internalized SPR and it rapidly increased afterwards, reaching a maximum value of 75.3% at about 30 min. At 90 min SPR-containing endosomes were mainly confined to the dendrites and the number of the internalized neurons began to decrease (58.1%). At 120 min 33.4% SPR-ir neurons had... |
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