Effects of substance P analogues on spinal dorsal horn neurons

Randić, Mirjana; Jeftinija, Srdija; Urbán, László; Raspantini, C.; Folkers, Karl

doi:10.1016/0196-9781(88)90178-7

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…Substance P containing afferents from primary sensory neurons project to second order neurons in the superficial layers of the spinal cord that normally receive nociceptive inputs (30,31). Release of substance P produces a strong and long lasting excitation of these spinal neurons and facilitates their activation by noxious stimulation (32)(33)(34)(35). Intrathecal injection of substance P causes scratching responses and caudally directed biting (36,37).…”

Section: Discussionmentioning

confidence: 99%

Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene

Zimmer

Baffi

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

198

103

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The tachykinin neuropeptides, substance P and substance K, are produced in nociceptive primary sensory neurons and in many brain regions involved in pain signaling. However, the precise role and importance of these neuropeptides in pain responses has been debated. We now show that mice that cannot produce these peptides display no significant pain responses following formalin injection and have an increased pain threshold in the hotplate test. On the other hand, the mutant mice react normally in the tail f lick assay and acetic acid-induced writhing tests. These results demonstrate that substance P and͞or substance K have essential functions in specific responses to pain.The tachykinins are a family of structurally related neuropeptides. In the mouse, they are encoded by the genes Tac1 and Tac2. Tac1 produces substance P, substance P (neurokinin A), neurokinin A (3-10), neuropeptide K, and neuropeptide ␥ as a result of differential splicing and posttranslational processing (1-4). Tac2 produces the peptide neurokinin B.The undecapeptide substance P was first detected by von Euler and Gaddum (5) in 1931. Its structure was revealed by Leeman and her coworkers (6, 7) in 1971. The Tac1 cDNA was cloned in 1983 by Nakanishi and his coworkers (2,8). The Tac1 gene is expressed in many regions in the central and peripheral nervous system, as well as in nonneuronal tissues. Substance P has been implicated in a variety of physiological processes including cardiovascular, respiratory, and gastrointestinal functions; inflammatory responses; and nociception. In addition, Hunt and coworkers have suggested that substance P may be involved in axon guidance during embryonic development (9).The precise role of substance P in these processes is unclear. For example, substance P is synthesized in nociceptive primary sensory neurons, which send C-and A␦ fibers to dorsal horn projection neurons in lamina I and IV-V, and to nociceptionspecific interneurons in lamina II-III of the spinal cord. Axons of projection neurons terminate in many supraspinal nuclei that are involved in pain transmission (10, 11). Nociceptive stimulation triggers the release of substance P from C-afferent terminals in the marginal layers of the spinal cord (12), evokes slow excitatory postsynaptic potentials in second-order sensory neurons in the dorsal horn, and facilitates their activation (13). These data, together with other functional evidence (11,14), indicated an important role for substance P in the processing of nociceptive signals.We have begun to use a genetic approach to study the functions of tachykinin peptides. As a first step, we have generated mice with a targeted mutation in the Tac1 gene. These mice are viable and fertile, but exhibit striking defects in nociceptive behaviors. MATERIALS AND METHODS Generation and Breeding of Tac1؊͞؊ Mice. Tac1 mutations were established by homologous recombination in MPI2 embryonic stem (ES) cells according to standard protocols (15). One mutant ES cell line was used to derive chimeras by morula aggrega...

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Section: Discussionmentioning

confidence: 99%

Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene

Zimmer

Baffi

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

198

103

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“…Comparison to tachykinin-mediated transmission in other systems Although there have been no previous studies of synaptic potentials evoked by individual SP-containing neurones, there are three well-characterized systems that have provided strong evidence of tachykinin-mediated slow synaptic transmission between neurones: the inferior mesenteric ganglion (1MG) of the guinea-pig (Konishi, Tsunoo & Otsuka, 1979;Konishi & Otsuka, 1985) the guinea-pig enteric nervous system (ENS) (Katayama & North, 1978;Johnson et al 1981;Bornstein et al 1984;Surprenant, 1984;Mihara et al 1985), and the dorsal horn of the rat spinal cord (Randic et al 1986(Randic et al , 1988. In each of these systems, there are abundant SP-positive presynaptic processes, calcium-dependent release of SP can be detected, and presynaptic stimulation evokes slow EPSPs that can be mimicked by responses to SP and blocked by desensitization to SP.…”

Section: Discussionmentioning

confidence: 99%

Substance P mediates synaptic transmission between rat myenteric neurones in cell culture.

Willard

1990

The Journal of Physiology

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SUMMARY1. Whole-cell patch-clamp recordings were made from pairs of neurones in cell cultures of rat myenteric neurones. In some pairs, action potentials evoked in the first neurone evoked a slow excitatory postsynaptic potential (EPSP) in the second neurone.2. Action potentials at a frequency of at least 5 Hz were required to evoke slow EPSPs. In one group of cells, the slow EPSP followed a series of nicotinic fast EPSPs; in another group, fast EPSPs did not precede the slow EPSP.3. The slow EPSPs were 2-16 mV in amplitude and were accompanied by decreased resting potassium conductance.4. Most (17/28) neurones in which action potentials evoked only slow EPSPs in a follower cell contained substance P (SP)-like immunoreactivity; they were not immunoreactive for 5-hydroxytryptamine (0/15) or vasoactive intestinal peptide (0/22

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“…Historically, such studies were performed using in vivo recordings (Brown et al, 1987; Carstens, 1997; Craig et al, 2001; Dickenson and Sullivan, 1986; Jinks and Carstens, 2000, 1999; Koerber et al, 1991; Randic et al, 1988; Torsney and Fitzgerald, 2002; Urch and Dickenson, 2003; Zhang et al, 2006). However, a considerable limitation to this approach is that it is difficult to target known cell types in the dorsal horn.…”

Section: Introductionmentioning

confidence: 99%

Semi-intact ex vivo approach to investigate spinal somatosensory circuits

Hachisuka

Baumbauer

Omori

et al. 2016

eLife

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The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons. Our findings suggest that spinal interneurons show distinct temporal and spatial tuning properties. We also show that modality selectivity — mechanical, heat and cold — can be assessed in both retrogradely labeled spinoparabrachial projection neurons and genetically labeled spinal interneurons. Finally, we demonstrate that interneuron connectivity can be determined via optogenetic activation of specific interneuron subtypes. This new approach may facilitate key conceptual advances in our understanding of the spinal somatosensory circuits in health and disease.DOI: http://dx.doi.org/10.7554/eLife.22866.001

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Effects of substance P analogues on spinal dorsal horn neurons

Cited by 13 publications

References 31 publications

Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene

Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene

Substance P mediates synaptic transmission between rat myenteric neurones in cell culture.

Semi-intact ex vivo approach to investigate spinal somatosensory circuits

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