The central and peripheral ends of the substance P-containing sensory neurones in the rat trigeminal system

1 The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2 Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3 Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-', i.a.), propranolol (0.5 mg kg', i.a.), atropine (0.5 mg kg', i.a.), methysergide (0.5 mg kg', i.a.) or mepyramine (10mg kg-', i.a.) plus cimetidine (10 mg kg-', i.a.), but both were significantly inhibited by pretreatment with capsaicin (50mg kg-', s.c.).4 Spantide (1-2tgmolkg-', i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5 Intra-arterial infusion of SP (0.5 Mmol kg-', i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6 Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release. 7 We suggest that SP and its receptors are mainly responsible for the vascular response induced by stimulation of the sectioned sciatic nerve, and that small-diameter afferent fibres containing SP tonically regulate vascular tone in cutaneous microvessels.

Section: Introductionmentioning

confidence: 98%

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw

Yonehara

Chen

Imai

et al. 1992

“…Meningeal a erents originating in the trigeminal ganglion (Mayberg et al, 1984;O'Connor & van der Kooy, 1986;Steiger & Meakin, 1984;Uddman et al, 1989) project mainly to the spinal trigeminal nucleus, where numerous substance P immunoreactive nerve ®bres were found particularly in the substantia gelatinosa (Cuello et al, 1978;Del Fiacco et al, 1983;Pearson & Jennes, 1988;Tashiro et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Release of immunoreactive substance P in the brain stem upon stimulation of the cranial dura mater with low pH – inhibition by the serotonin (5‐HT₁) receptor agonist CP 93,129

Meßlinger¹,

Ebersberger²,

Schaible³

1998

1 The therapeutical bene®t of serotonin (5-HT 1 ) receptor agonists in the treatment of migraine headache has been attributed to their inhibitory e ect on the release of pro-in¯ammatory neuropeptides from trigeminal a erents within the cranial meninges. The e ect of 5-HT 1 receptor agonists on the release of neuropeptides from central a erent terminals has not been examined so far. In the present study in the rat we therefore measured the e ect of the 5-HT 1B receptor agonist CP 93,129 on the stimulation-evoked release of immunoreactive substance P (ir-SP) in the spinal trigeminal nucleus. 2 To measure release of ir-SP, microprobes coated with antibody to substance P were inserted into the medulla oblongata at the level of the obex. The ipsilateral parietal dura mater encephali was exposed and stimulated with acid phosphate bu ered Tyrode solution (pH 5.8). This chemical stimulus increased the release of ir-SP in the medullary dorsal horn. 3 Systemic (i.v.) administration of CP 93,129 (460 nmol kg 71 ) prior to stimulation suppressed the stimulation-evoked increase of release of ir-SP. Local administration of CP 93,129 (10 mM) to the dorsal surface of the medulla had no signi®cant inhibitory e ect on the release. 4 It is concluded that systemically applied 5-HT 1 receptor agonists reduce the stimulation-evoked release of substance P from the central endings of meningeal a erents in the spinal trigeminal nucleus (medullary dorsal horn). This inhibitory e ect may contribute to the antinociceptive e ect of 5-HT 1 receptor agonists in migraine.

“…Immunohistochemical and neurochemical evidence indicates that substance P is present in the peripheral as well as the central terminals of some primary afferent neurones (Hokfelt, Kellerth, Nilsson & Pemow, 1975; Cuello, Del Fiacco & Paxinos, 1978) and it is conceivable, therefore, that substance P is released from these neurones in the skin and other organs. It has been proposed that substance P, released from sensory nerve endings, plays a part in the triple response of skin to an injury (Hagermark et al, 1978;), and we have already pointed out that the flare, which is believed to be mediated by the so-called 'axon reflex' in the triple response, is induced only by those peptides which also release histamine from rat mast cells in vitro (Foreman & Jordan, 1981).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Neurotensin With the Substance P Receptor Mediating Histamine Release From Rat Mast Cells and the Flare in Human Skin

Foreman

Jordan

Piotrowski

1982

1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 DIM.2 At concentrations in the range 2.5 to 10 EM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin,2.5 to 10 lM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP411) all inhibited histamine release by substance P, but physalaemin did not.5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin.6 [D-Trp7'9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7'9]SP1_1j also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.