Pain
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A comparison was made of spontaneous nociceptive behaviors elicited by subcutaneous injection of formalin (0.5-10.0%) into the plantar or dorsal surface of the right hindpaw in rats. In the present study, we also examined the effect of paw formalin injection on the release of nitric oxide (NO) metabolites (nitrite/nitrate) and glutamate from the spinal cord in anesthetized rats using a dialysis probe placed in the lumbar subarachnoid space. Two distinct quantifiable behaviors indicative of pain were identified by formalin injected into both regions of the paw. ⋯ A significant increase of glutamate was observed in the 0-10 min samples obtained after injection of formalin (5.0%) into the plantar and dorsal surface of the paw, whereas 0.5 and 10.0% formalin induced no substantial release. These results suggest that 5.0% formalin should be used when studying antinociceptive activity of NO- and N-methyl-D-aspartate-related compounds in the formalin test in rats. Formalin injection into the plantar surface of the paw might prove to be useful for evoking the licking/biting response, particularly in the early phase.
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Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. ⋯ Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.
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Neuropathic pain, due to peripheral nerve damage, can include allodynia (perception of innocuous stimuli as being painful), hyperalgesia (increased sensitivity to noxious stimuli) and spontaneous pain, often accompanied by sensory deficits. Plasticity in transmission and modulatory systems are implicated in the underlying mechanisms. The Kim and Chung rodent model of neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of the sciatic nerve and reproducibly induced mechanical and cold allodynia in the ipsilateral hindpaw over the 14 day post-operative period. ⋯ After neuropathy the potency of omega-conotoxin-GVIA was increased at lower doses in comparison to control. This indicates an altered role for N-type but not P-type VDCCs in sensory transmission after neuropathy and selective plasticity in these channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important.
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The present study aimed to elucidate the distribution of gamma-aminobutyric acid (GABA) transporters in the spinal trigeminal nucleus after carrageenan injections. Dense GAT-1 and GAT-3 but very little GAT-2 immunoreactivity was observed in the normal rat spinal trigeminal nucleus. The GAT-1-positive glial cells in the normal rat spinal trigeminal nucleus contained dense bundles of glial filaments and had features of astrocytes. ⋯ Electron microscopy showed that transporter immunoreactivity in the spinal trigeminal nucleus of carrageenan-injected rats was predominantly present in glial processes, showing that the increase in the number of processes observed at light microscopy was due to increased immunoreactivity in glial processes. An increased expression of GABA transporters in the carrageenan-injected spinal trigeminal nucleus could therefore result in a faster removal of GABA from the synaptic cleft of GABAergic axon terminals compared to normal rats. This could result in reduced inhibition/increased activity of the trigeminothalamic neurons in the spinal trigeminal nucleus, and could contribute to hyperalgesia after carrageenan injections.
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The analgesic actions of opioids are in large part mediated by activation of brainstem pain modulating neurons that depress nociceptive transmission at the level of the dorsal horn. The present study was designed to characterize the contribution of N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated excitatory transmission within the rostral ventromedial medulla (RVM) to the activation of brainstem inhibitory output neurons and analgesia produced by systemic morphine administration. The NMDA receptor antagonist D-2-amino-5-phosophonopentanoic acid (AP5), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) or saline was infused into the RVM of lightly anesthetized rats while recording the activity of identified pain modulating neurons: 'off-cells', thought to inhibit nociceptive transmission, and 'on-cells', thought to facilitate nociception. ⋯ This excitatory process may play a role in the analgesic synergy produced by simultaneous mu-opioid activation at different levels of the neuraxis. Second, reflex-related activation of on-cells is mediated by a non-NMDA receptor, and this activation does not appear to play a significant role in regulating reflex responses to acute noxious stimuli. Excitatory amino acid-mediated excitation thus has at least two distinct roles within the RVM, activating off-cells and on-cells under different conditions.