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Z Khalil

Publications and source records attributed to Z Khalil.

At least 37 records · Page 2Linked to original sources
PubMed1998

CGRP and nitric oxide of neuronal origin and their involvement in neurogenic vasodilatation in rat skin microvasculature.

1. Sensory nerves are important for the initiation of neurogenic inflammation and tissue repair. Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been implicated in neurogenic vasodilatation and inflammatory responses. 2. A blister model in the rat hind footpad was used as a site to induce neurogenic vasodilatation in response to antidromic electrical stimulation of the sciatic nerve. Blood flux was monitored with a laser Doppler flow monitor. 3. The quantitative contributions of CGRP and NO to vasodilatation were examined by use of the CGRP receptor antagonist CGRP8-37 and NO synthase inhibitors 7-nitroindazole (7-NI), 3-bromo 7-NI and N(G)-nitro L-arginine methyl ester (L-NAME). The potential modulatory role of endothelin was examined by use of the ET(A) receptor antagonist BQ-123. 4. CGRP8-37 (10 microM) was perfused over the blister base before nerve stimulation and continuously throughout the post-stimulation period, resulting in a significant reduction (41%) in the blood flux vascular response. 5. Pretreatment with the specific neuronal NO synthase inhibitors, 7-NI and 3-bromo 7-NI (10 mg kg(-1), i.v.), and of the non-specific L-NAME (100 microM), resulted in significant inhibition of the blood flux response (36%, 72% and 57% decrease, respectively). In contrast, 7-NI treatment in young rats pretreated with capsaicin had no further effect on the vascular response, suggesting that the source of NO is the sensory nerves. 6. BQ-123 (10 microM) significantly enhanced the stimulation-induced blood flux response (61% increase). When 7-NI was co-administered with either CGRP8-37 or BQ-123, the drug actions were additive, suggesting that there was no interaction between NO and CGRP or endothelin. 7. These data suggest that both NO and CGRP participate in neurogenic vasodilatation in rat skin microvasculature and that this response is modulated by endogenous endothelin.

Animals↗
PubMed1997

Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

Adult↗
PubMed1997

[The effect of endothelin and protein kinase C on the vasoactive mechanisms of beta A(4)25-35 at skin microvasculature].

OBJECTIVE: The aim of the present study is to investigate the mechanisms of beta A(4)25-35 at the level of skin microvascula ture. METHODS: Using a blister model in rat skin, we examined the possibilities that beta A(4)25-35 induces VC effect via the release of endothelin and the involvement of protein kinase C (PKC). Changes in microvascular blood flow were monitored using laser Doppler flowmetry and the area within the response curve measured. RESULTS: The results showed that either the endothelin receptor antagonist (BQ--123 at 10 mumol) or PKC inhibitor (bisindolylmaleimide at 1 mu mol) was perfused before beta A(4)25-35. It prevented beta A(4)25-35 from inducing a VC effect and allowed a subsequent SP to induce a normal response. CONCLUSION: Both endothelin and PKC play a role in the mechanism be which beta A(4)25-35 induces VC effect and modulates subsequent SP response at the level of skin microvasculature. We suggest the possibility that the vascular activity of beta A(4)25-35 could be mediated via endothelin with subsequent activation of PKC.

Alzheimer Disease↗
PubMed1996

Mechanisms underlying the vascular activity of beta-amyloid protein fragment (beta A(4)25-35) at the level of skin microvasculature.

Deposition of beta-amyloid protein (beta A4) in extracellular senile plaques is a pathologic hallmark of Alzheimer's disease (AD). The neurotoxic effect of beta A4 has been ascribed to a discrete 11-amino acid internal sequence (beta A(4)25-35). Substance P (SP) has been found to be depleted in the brain of AD patients while its presence was found to protect against the neurodegenerative effect of beta A(4)25-35. Our previous studies, in vivo, in aged rats showed that beta A(4)25-35 exhibits a potent vasoconstrictor (VC) effect in rat skin microvasculature and can prevent SP but not calcitonin gene-related peptide (CGRP) from inducing a vasodilator (VD) response. It was postulated that beta A(4)25-35 might be interacting with SP at the level of the second messenger system via the phosphoinositide pathway. Using a blister model of inflammation in the rat hind footpad, we examined the ability of beta A(4)25-35 to modulate the vascular activity of bradykinin (BK) and serotonin (5-HT) which also activate the phosphoinositide pathway. In addition, the role of nitric oxide (NO), endothelin (ET, an endothelium-derived constrictor factor) and protein kinase C (PKC) in the vascular effects of beta A(4)25-35 were examined using the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG), the ET-receptor antagonist, BQ-123, and the PKC inhibitor, bisindolylmaleimide (BIM) respectively. Changes in microvascular blood flow were monitored using laser Doppler flowmetry and the area within the response curve measured. The results showed that beta A(4)25-35 (10 microM) induced a VC effect and inhibited the subsequent VD response to BK (10 microM) and 5-HT (1 microM) in a similar fashion to its effect on SP (1 microM). In the presence of L-NOARG (100 microM), the VD effect of SP was reduced and further attenuated after perfusion of beta A(4)25-35. Superfusion of the blister base with BQ-123 (10 microM) or BIM (1 microM) prior to and during perfusion with beta A(4)25-35 abolished its VC effect and allowed SP to induce a normal VD response in both young and old rats. Based on these results, we suggest that the vascular activity of the active fragment, beta A(4)25-35, is mediated by ET via activation of PKC. This study provides new findings which may help to elucidate the signal transduction mechanisms involved in the vascular activity of beta A(4)25-35. The relevance of these mechanisms to those underlying the pathological effects of beta A4 and their significance in AD remains to be determined.

Aging↗
PubMed1996

Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin.

A supersensitivity to the neuropeptide substance P (SP) has been shown to develop in post-terminal membranes of many denervated tissues. This study examined changes in the sensitivity of post-terminal vascular receptors to SP and calcitonin gene-related peptide (CGRP) in rat skin microvasculature following sciatic nerve section. In anaesthetised rats, 0.5 cm of sciatic nerve in the right mid-thigh region was removed. Two weeks later, SP (100 microM) and sodium nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced into denervated intact footpad skin, via the electrophoresis technique. Laser doppler flowmeter was used to record changes in relative blood flow in the rat hind footpad. The results showed a significant increase in SP response over controls and slight increase in smooth muscle reactivity as determined by an increase in the vascular response to SNP. In another set of experiments, the sensitivity of post-terminal receptors was examined over a 4 weeks period in an acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced blister was raised on the hind footpad and SP, CGRP (each at 1 microM) or SNP (100 microM) were superfused over the blister base. In nerve lesioned rats, using the acutely injured footpad skin model, the results showed a reduction in the vascular responses to SP, CGRP and SNP. The response to SP continued to decrease over time reaching 22% of control values by 4 weeks. Responses to SNP and CGRP were reduced to 53% and 45% respectively by 2 weeks and then improved to 75% of control values by 4 weeks. Possible contributions of sympathetic efferents and the saphenous nerve to these reduced responses in acutely injured skin of nerve lesioned rats were examined using guanethidine (50 mg/kg i.p.) or sectioned saphenous nerve respectively. These procedures did not significantly modify the reduced vascular responses in the blister base of lesioned rats. Possible activation of endogenous opioids and/or the release of endothelin due to blister induction in nerve lesioned rats was examined using naloxone and the endothelin receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP response in lesioned rats to 41% of control value with no change in smooth muscle reactivity. BQ-123 significantly increased the responses to SP and SNP to 51% and 100% of their own control values respectively. It is concluded that supersensitivity of post-terminal vascular receptors develops in intact skin following chronic nerve lesion. On the other hand, acute injury of the denervated skin area induces activation of endogenous inhibitory modulatory mechanisms that masks this supersensitivity.

Anesthesia↗
PubMed1996

Sensory peptides as neuromodulators of wound healing in aged rats.

An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system with age could be a contributing factor for delayed wound healing in the elderly. This study was designed to examine the role of sensory nerves (using capsaicin-pretreated rats) and the effect of aging on the healing of a thermal wound induced on the interscapular region (using a CO2 laser). The healing endpoint was the time when full wound contraction had occurred. The ability of the sensory peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in modulating wound healing in aged rats was examined by taking into account the modulatory interaction effects between these peptides. A blister model in the rat hind footpad combined with a laser Doppler flowmeter was used initially to establish these vascular interaction effects. The results showed a significant delay in thermal wound healing in both the capsaicin-treated and aged rats. Using the blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged vasodilator response, respectively. When tested together, SP attenuated the vascular effect of CGRP, an effect that was reversed using the tachykinin antagonist spantide II. When injected at the wound site, SP and CGRP were equally potent in promoting wound healing in aged rats. The beneficial effect of taking the interaction effects into account was most evident in a group of rats that received the tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete wound closure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged controls. We contend that would healing in aged rats can be accelerated by exogenous administration of sensory peptides. Furthermore, modulatory interaction effects between sensory peptides should be taken into consideration when designing any treatment protocol that purports to accelerate wound healing.

Aging↗
PubMed1996

[Family physicians and scientific information. Survey on hypertension and diuretics].

In order to analyse the quality of scientific communication in the field of hypertension, we have conducted a survey among French physicians. The topics of the questions were partly related to hypertension and partly to diuretics; 3,600 questions forms have been mailed: 610 answers were returned (17%). The results show that most of physicians are unsufficiently informed about primary prevention therapeutical trials and recommendations. Moreover, whereas all physicians questionned (97%) consider that diuretics constitute a current therapeutic approach, this class remains largely unknown concerning its mechanisms, efficacy and tolerance dose relationships. As 80% of general practitioners having participated to this survey wish to be more informed on recent data in this field, these results emphasize the necessity of adapting information to the need of practitioners, raise questions concerning the information supports, the role of scientific committees in the medical information and the necessity to complete clinical research by studies which results may be rapidly applicable in clinical practice.

Adult↗
PubMed1995

Role of nitric oxide in the actions of substance P and other mediators of inflammation in rat skin microvasculature.

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N(G)-nitro-D-arginine was without effect. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.

Adenosine Triphosphate↗
PubMed1994

Beta A4(25-35) modulates substance P effect on rat skin microvasculature in aged rats: pharmacological manipulation using SEC-receptor ligands.

The primary constituent of the senile plaque core in Alzheimer's disease (AD) is the beta-amyloid protein (beta A4). A discrete 11 amino acid fragment of the beta A4, beta A4(25-35), has been implicated in mediating in vitro neurotoxicity and an inflammatory response surrounding senile plaques in AD via interaction with the Serpin Enzyme Complex (SEC) receptor. Substance P (SP), a neuropeptide of the tachykinin family and a major mediator of neurogenic inflammation, shows sequence homology to beta A4(25-35) and has been shown to protect against the neurotoxicity of beta-amyloid. SP also competes with beta A4(25-35) for binding to the SEC-receptor. SP neurons have also been found to be depleted in AD. Using a blister model of inflammation in the rat hind footpad, we have examined the effect of beta A4(25-35) and its interaction with SP in rat skin microvasculature and determined age-related changes to these phenomena. In addition, pharmacological manipulation of these responses using SEC-receptor ligands (peptide 105Y and 105C) was also undertaken. Because of the evidence for co-existence and co-release of SP and calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory nerves, it was of interest to examine the interaction of CGRP with beta A4(25-35) on rat skin microvasculature. beta A4(25-35) (10 microM) was perfused over the base of a blister raised on the hind footpad of anaesthetised young and old rats. This was followed by perfusion of SP (1 microM) or CGRP (1 microM) after Ringer's solution. Relative blood flow was monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Peptides↗
PubMed1994

Effects of ageing on sensory nerve function in rat skin.

Human studies have shown an age-related decrease in modulation of skin vascular reactivity by sensory nerves that correlates with a decline in wound repair efficacy. Using a vacuum-induced blister model in the rat hind footpad, we have investigated age-related changes in pre- and post-terminal activity of primary afferents involved in skin neurovascular function. Changes in local skin blood flow were monitored using a laser Doppler flowmeter. Pre-terminal stimulation was achieved by electrical stimulation of the distal end of the sciatic nerve (10 V, 15 Hz and 0.5 ms) in three groups of young, old and neonatally pretreated capsaicin rats (3, 24 and 3 months old, respectively). The effect of post-terminal stimulation, achieved using local perfusion of 1 microM substance P (SP) over the blister base, was examined in young (3 months old), mature (12 months old) and aged (24 months old) rats. In addition to changes in SP responsiveness, other post-terminal changes studied included changes in smooth muscle reactivity to sodium nitroprusside (SNP), which acts directly on smooth muscle and to endothelial cell function using N-nitro-L-arginine (L-NORAG), a selective inhibitor of nitric oxide synthesis and endothelium-dependent relaxation. Electrical stimulation of the sciatic nerve in young rats induced an increase in local blood flow (within 1 min) that was maintained during the stimulation period, while the capsaicin group and the old group showed a significantly increased latency and decreased amplitude of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

The quantitative contribution of nitric oxide and sensory nerves to bradykinin-induced inflammation in rat skin microvasculature.

Using a blister model in the rat hind footpad, the present study undertook to examine the relative contribution of sensory nerves and nitric oxide (NO) to the inflammatory response induced by bradykinin (BK). Using this model, combined with laser Doppler flowmetry, we were able to simultaneously monitor two parameters of the inflammatory response, namely vasodilatation (VD) and plasma extravasation (PE). Perfusion of BK (1, 10 or 100 microM) over the blister base elicited both VD and PE responses which were dose-dependent. The VD response was of rapid onset, sustained at the lowest concentration (1 microM), and showed tachyphylaxis at the highest two concentrations (10 and 100 microM). The PE response, however, was delayed in onset at the lower concentration but the response was maintained at all concentrations. The endothelium-independent vasodilator, sodium nitroprusside. (SNP, 100 microM), was used as an internal control and elicited a rapid maintained VD response. In rats pretreated as neonates with capsaicin to destroy primary sensory afferents, the inflammatory response to 10 microM BK was significantly smaller (50% and 64% decrease in VD and PE, respectively). The selective inhibitor of NO synthase, NG-nitro-L-arginine (L-NORAG) at 100 microM significantly attenuated the inflammatory response to BK in control rats (76% and 60% decrease in VD and PE, respectively) with a further decrease in the response in capsaicin pretreated rats. The inactive stereoisomer NG-nitro-D-arginine (D-NORAG) (100 microM) did not affect the inflammatory response to BK. The vasodilator response to SNP was intact in capsaicin pretreated rats and was not affected by either L-NORAG or D-NORAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1992

Nitric oxide and sensory nerves are involved in the vasodilator response to acetylcholine but not calcitonin gene-related peptide in rat skin microvasculature.

1. The contributions of sensory nerves and nitric oxide (NO) to vasodilator responses to acetylcholine (ACh) and calcitonin gene-related peptide (CGRP) were examined in rat skin microvasculature with a laser Doppler flowmeter to monitor relative blood flow. 2. Perfusion of ACh (100 microM; for 30 min) over a blister base on the rat hind footpad elicited microvascular vasodilatation and this response was not sustained. CGRP (1 microM; 10 min perfusion) also elicited vasodilatation and this response was maintained even when CGRP was no longer in contact with the blister base. 3. The vasodilator response to ACh was significantly smaller in rats pretreated as neonates with capsaicin to destroy primary sensory afferents than it was in age-matched controls. The vasodilator response to CGRP was unaffected by capsaicin pretreatment. 4. Selective inhibitors of NO synthase, NG-nitro-L-arginine (L-NOARG) and NG-monomethyl-L-arginine (L-NMMA) (both at 100 microM) attenuated the vasodilator response to ACh in control rats, but had no effect on the vasodilator response to CGRP. There was a significant L-NOARG-resistant component in control rats while in capsaicin-treated rats the vasodilator response to ACh was virtually abolished by L-NOARG. The inactive stereoisomer NG-monomethyl-D-arginine (100 microM) did not affect the vasodilator response to ACh. 5. The efficacy of L-NOARG and L-NMMA as inhibitors of endothelium-dependent responses was confirmed by use of an endothelium-dependent vasodilator, the calcium ionophore A23187 (100 microM; 10 min perfusion). Vasodilatation to A23187 was strongly attenuated by both L-NOARG and L-NMMA.6. These results suggest that sensory nerves and NO are both involved in the dilatation produced by ACh in rat skin microvasculature. A component of the vasodilator response elicited by ACh involves a direct action on the microvascular endothelium with subsequent generation of NO, while an additional component is elicited via activation of sensory nerves. The vasodilator mediator(s) released by ACh from sensory nerves acts largely independently of NO.7. The vasodilator response to CGRP is independent of a prejunctional action on sensory nerves and of NO.

Acetylcholine↗
PubMed1990

Neural pathways in chronic pain.

The evidence for changes in function of the central nervous system in cases of chronic pain is persuasive. We are not dealing with a passively wired system but one which changes structure and function and even connectivity in response to incoming sensory information. Whether these changes are capable of reversal with time and treatment remains to be shown. An optimist would suggest that physiological changes without abnormalities are indeed capable of reversal given time and appropriate neural input that matches normal non-painful afferent stimulation. That this is feasible is suggested by strategies of management with successful outcomes in patients with chronic pain, especially when pain is due to intermittent or limited ongoing stimulation of nociceptors. Clinical experience suggests, however, that deafferentation pain syndromes where pain is a consequence of damage directly to the nervous system cannot be viewed in such an optimistic light. A great deal more knowledge is required of how both the peripheral and central nervous system react to damage before we will be in a position to manage this source of chronic pain successfully.

Afferent Pathways↗
PubMed1990

Serotonin modulates substance P-induced plasma extravasation and vasodilatation in rat skin by an action through capsaicin-sensitive primary afferent nerves.

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine the ability of serotonin (5-HT) to modulate an inflammatory reaction manifested as plasma extravasation and vasodilatation induced by the neuropeptide substance P (SP). In addition, the role of primary afferent sensory nerve fibres in these modulatory effects was studied in capsaicin pretreated rats. Using a protocol of simultaneous perfusion of amine and peptide over the blister base, no major modulatory effect was observed. On the other hand, using a protocol of sequential perfusion, 5-HT was found to extend the plasma extravasation and vasodilatation responses to SP. 5-HT maintained the plasma extravasation response to SP after cessation of stimulation (during the post-stimulation period). On the other hand, it extended the vasodilatation response to SP during the actual stimulation period by preventing the occurrence of tachyphylaxis. These modulatory effects were absent in capsacin-pretreated rats. The present study provides evidence for the first time in vivo to suggest that serotonin can modulate an inflammatory response to SP via a mechanism that involves capsaicin-sensitive sensory fibres.

Afferent Pathways↗
PubMed1990

Modulation of a peripheral inflammatory response to substance P by locally administered opioid receptor agonists.

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine possible peripheral effects of specific mu (DAGO) and delta (DSLET) opioid receptor agonists on an inflammatory response induced by substance P, the putative mediator of neurogenic inflammation. When perfused over the blister base, SP induced both plasma extravasation and vasodilatation responses. These responses were significantly inhibited in the presence of either opioid receptor agonist in a naloxone reversible manner. DSLET inhibited SP responses in a dose dependent manner and was 100 times more potent than DAGO. The role of primary afferent sensory nerve terminals in these modulatory effects was investigated in rats pretreated as neonates with capsaicin. The ability of DAGO and DSLET to inhibit the inflammatory response in these rats was significantly less than that in controls. The data raises the possibility that the inhibitory effect of the opioid receptor agonists on the inflammatory response might reflect a role for opioids in modulating tachyphylaxis to SP.

Administration, Topical↗
PubMed1989

Sequence of events in substance P-mediated plasma extravasation in rat skin.

Using a blister model of inflammation in the rat hind footpad, we have studied the temporal and quantitative contribution of mast cell mediators and prostaglandins to substance P-induced plasma extravasation. In addition substance P-related peptides (neurokinin A, SP5-11 and SP1-7) were tested for their ability to induce a plasma extravasation response and the extent of histamine involvement to the response was determined. The present results show that the plasma extravasation response to substance P consists of an early substance P-mediated response that is independent of other mediators and a late response that involves interaction between substance P, mast cell mediators and prostaglandins. An early histamine-independent response was also mediated by neurokinin A, a tachykinin that shares a common C-terminal with substance P and by a C-terminally directed analogue of substance P, namely SP5-11. On the other hand, a late histamine-dependent response was mediated by the N-terminally directed analogue, SP1-7. The present data are suggestive of a possible sequence of events that might occur during an inflammatory response to substance P and might involve independent actions of its C- and N-terminal.

Animals↗
PubMed1989

Involvement of capsaicin-sensitive afferent nerve fibres in serotonin-induced plasma extravasation and vasodilatation in rat skin.

We have investigated the ability of serotonin (5-HT) to induce an inflammatory reaction manifested as plasma extravasation and vasodilatation responses in a blister model in the rat hind footpad. The involvement of unmyelinated sensory fibres in these responses was investigated using capsaicin pretreated rats. 5-HT (0.1-10 microM), when perfused over the blister base, induced both plasma extravasation and vasodilatation responses in a dose-dependent manner. Both the plasma extravasation and the vasodilatation responses were maintained throughout a 30 min stimulation period. Neonatal capsaicin treatment resulted in a 78% and 56% reduction in the plasma extravasation and vasodilatation responses, respectively. The present results provide evidence for the involvement of capsaicin-sensitive sensory nerves in 5-HT-mediated plasma extravasation and vasodilatation responses in the rat.

Animals↗