Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

Abstract

Objectives: Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet. Methods: Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated. Results: Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision. Conclusion: In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.

Involvement of Neuropeptide Y in Post-Incisional Nociception in Rats

“…Thus, neuronal activity, immediately after incision, would be more prolific than at day 5 after incision is understandable. Alteration in SP expression in the superficial laminae has been previously reported after paw incision [23]. Again, Ji et al [20] had reported an increase in NPY immunoreactivity in lamina II after peripheral inflammation, localized to the medial part of the dorsal horn.…”

“…Furthermore, these neurons co-express GABA and thus are inhibitory in nature [7,22]. Selective expression of other neuropeptides associated with nociception like SP and calcitonin gene-related peptide were also noted in these laminae [23,24]. Even μ-opioid receptors, the opioid receptor subtype binding to morphine are also noted in this region [25].…”

“…However, neuropeptides are initially synthesized in precursor forms like Prepro-NPY, which are unsuitable for release, despite persistent volleys of action potentials. Incidentally, these precursor forms are recognized by polyclonal antibodies [23]. Restoration of the NPY level was interrupted on day 1, when its expression decreased again.…”

The Effect of Aging on Nerve Morphology and Substance P Expression in Mouse and Human Corneas

“…9,10 Among neurokinin receptors, Neurokinin 1 receptor is expressed mainly on neuronal and immune cells, [11][12][13][14] and it has the highest affinity for SP. 15 SP is expressed at a high concentration in the central and peripheral nervous system, [16][17][18] and it plays a crucial role in neuronal tropism 19 and in sensitivity/nociception 20 via the neuronal NK1 receptor. 18,20,21 In the cornea, the functions of SP have just started to emerge; they are diverse and involve the regulation of wound healing and inflammation.…”

“…15 SP is expressed at a high concentration in the central and peripheral nervous system, [16][17][18] and it plays a crucial role in neuronal tropism 19 and in sensitivity/nociception 20 via the neuronal NK1 receptor. 18,20,21 In the cornea, the functions of SP have just started to emerge; they are diverse and involve the regulation of wound healing and inflammation. In particular, SP plays a key role in maintaining sub-basal corneal nerve plexus organization, possibly through an autocrine loop on nerve cells.…”