Abstract
BackgroundThere is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. Although it has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive) primary afferents, we know little about their responses to noxious stimuli. In this study we have looked for phosphorylation of extracellular signal-regulated kinases (ERKs) in these neurons in response to different types of noxious stimulus applied to one hindlimb of anaesthetised rats. The stimuli were mechanical (repeated pinching), thermal (immersion in water at 52°C) or chemical (injection of 2% formaldehyde).ResultsFive minutes after each type of stimulus we observed numerous cells with phosphorylated ERK (pERK) in laminae I and IIo, together with scattered positive cells in deeper laminae. We found that virtually all of the lamina III/IV NK1r-immunoreactive neurons contained pERK after each of these stimuli and that in the great majority of cases there was internalisation of the NK1r on the dorsal dendrites of these cells. In addition, we also saw neurons in lamina III that were pERK-positive but lacked the NK1r, and these were particularly evident in animals that had had the pinch stimulus.ConclusionOur results demonstrate that lamina III/IV NK1r-immunoreactive neurons show receptor internalisation and ERK phosphorylation after mechanical, thermal or chemical noxious stimuli.
Highlights
There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae
We have shown that the large lamina III/IV NK1r-expressing cells are strongly innervated by substance P-containing primary afferents, which form numerous synapses on their dendrites and cell bodies [18]
Since the large lamina III/IV NK1r neurons provide a strong monosynaptic connection from substance P-containing afferents to brain regions involved in pain perception, such as the lateral parabrachial area and thalamus [13,15,18], it is likely that phosphorylation of extracellular signal-regulated kinases (ERKs) in these cells plays a significant part in inflammatory pain
Summary
There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. It has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive) primary afferents, we know little about their responses to noxious stimuli. We have shown that the large lamina III/IV NK1r-expressing cells are strongly innervated by substance P-containing primary afferents, which form numerous synapses on their dendrites and cell bodies [18]. This suggests that they would be strongly activated by noxious stimulation. Doyle and Hunt [20] reported that while 40% of these cells up-regulated the transcription factor fos in response to a subcutaneous injection of formalin, few of them expressed fos after other types of noxious stimulus, including noxious thermal stimulation
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