RESUMO
OBJECTIVE AND DESIGN: The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test. METHODS: The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice. RESULTS: Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain. CONCLUSION: These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dor/prevenção & controle , Prostaglandina-Endoperóxido Sintases/metabolismo , Acetaminofen/uso terapêutico , Animais , Dipirona/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Formaldeído/farmacologia , Temperatura Alta , Masculino , Camundongos , Camundongos Endogâmicos , Dor/induzido quimicamente , Medição da Dor/métodosRESUMO
To enhance analgesia, combination of analgesics drugs of proven efficacy is a strategy which is accompanied by a reduction of adverse effects. The present study was undertaken to characterize the antinociceptive interaction of morphine with different non-steroidal anti-inflammatory drugs (NSAIDs) using isobolographic analysis and the writhing test of mice. One of the possible mechanisms of action of spinally administered morphine with non-steroidal antiinflammatory drugs was investigated using the DOR antagonist naltrindole. The study demonstrated a synergistic antinociception of spinal administered combinations of morphine with the following NSAIDs agents: diclofenac, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam. The supraadditive effect seems to be independent of the selectivity of each NSAIDs to inhibit COX-1 or COX-2. The findings of the present work suggest that the combinations of opioids and non-steroidal anti-inflammatory drugs have a direct action on spinal processing of the nociceptive information, which may achieved by additional mechanisms independent of prostaglandin synthesis inhibition and/or activation of opioid receptors. The lack of effect of naltrindole to modify the analgesic activity of the combination of opioids and NSAIDs indicates that others pain regulatory systems are involved in this central action. Therefore, these combinations could be a viable alternative to clinical pain management, especially trough multimodal analgesia.
Assuntos
Analgésicos Opioides/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Morfina/farmacologia , Naltrexona/análogos & derivados , Receptores Opioides delta/fisiologia , Medula Espinal/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Animais , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/uso terapêutico , Sinergismo Farmacológico , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos , Morfina/administração & dosagem , Morfina/uso terapêutico , Naltrexona/administração & dosagem , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Dor/tratamento farmacológico , Dor/fisiopatologia , Receptores Opioides delta/antagonistas & inibidores , Medula Espinal/fisiopatologiaRESUMO
The antinociceptive activity of dexketoprofen was studied in mice using the formalin assay for orofacial pain. The interaction between dexketoprofen and co-administered tramadol was studied using isobolographic analysis. The intraperitoneal administration of dexketoprofen or tramadol, showed dose-dependent antinociceptive activity in both phases of the assay. When administered together, the interaction was mildly synergistic during the first phase, and antagonistic in the second phase. Selective opioid receptor antagonists where used in order to measure the analgesic activity of tramadol in other regions of the CNS. The co-administration of dexketoprofen and tramadol, with previous administration of naltrexone, showed high synergistic activity during the first phase, and less but still synergistic during the second. When using naltrindole, the interaction was mildly more synergistic than the mixture dexketoprofen+tramadol during both phases. Using norbinaltorphimine, the interaction was synergistic in both phases, more marked in the second. These results suggest that the opioid activity of tramadol has an inhibiting effect in antinociceptive activity of the interaction between dexketoprofen and tramadol during the inflammatory (late) stages of pain.
Assuntos
Analgésicos/uso terapêutico , Cetoprofeno/uso terapêutico , Antagonistas de Entorpecentes/farmacologia , Dor/tratamento farmacológico , Tramadol/uso terapêutico , Analgésicos/farmacologia , Animais , Sinergismo Farmacológico , Cetoprofeno/farmacologia , Masculino , Camundongos , Antagonistas de Entorpecentes/administração & dosagem , Dor/induzido quimicamente , Tramadol/farmacologiaRESUMO
The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clonidine and each nonsteroidal anti-inflammatory drugs, when coadministered intraperitoneally and intrathecally (i.t.). The simultaneous intraperitoneal administration of fixed ratios of ED(50) fractions of all nonsteroidal anti-inflammatory drugs (naproxen, piroxicam, paracetamol, dipyrone or metamizol and nimesulide) combined with clonidine resulted in synergistic interactions. The same combinations administered intrathecally were additive. The synergistic interactions between systemic nonsteroidal anti-inflammatory drugs and clonidine may involve supraspinal mechanisms.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Clonidina/farmacologia , Medição da Dor/efeitos dos fármacos , Analgésicos/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Clonidina/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Quimioterapia Combinada , Feminino , Injeções Intraperitoneais , Injeções Espinhais , Masculino , Camundongos , Medição da Dor/métodosRESUMO
The antinociceptive activity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained mainly on the basis of their inhibition of the enzyme cyclooxygenase (COX); however, this inhibition is not enough to completely explain the analgesic efficacy of these drugs. The modulation exerted by serotonergic systems on antinociception is well known. The purpose of the present work was to further explore the role of serotonin in the antinociceptive activity of NSAIDs using the writhing test and the tail-flick test of the mice after the inhibition of serotonin biosynthesis with intraperitoneal p-chlorophenylalanine (p-CPA). Pretreatment with p-CPA produced a significant decrease in the antinociceptive activity of NSAIDs administered either by the intraperitoneal or intrathecal routes, in both algesiometric tests. These results suggest a complementary mechanism of antinociception for NSAIDs, independent of their ability to inhibit the activity of COX, involving the activation of descending serotonergic pathways. By the pharmacological nature of the study, one limitation was the absence of biochemical measurement of the synthesis of 5-HT, since the reduction of the brain 5-HT synthesis by pretreatment with p-CPA will be expressed as a diminished antinociceptive activity of NSAIDs, which would be a new argument to consider NSAIDs acting as central analgesic agents.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medição da Dor/efeitos dos fármacos , Dor/metabolismo , Serotonina/biossíntese , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Fenclonina/farmacologia , Masculino , Camundongos , Tempo de Reação/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Fatores de TempoRESUMO
The nonsteroidal anti-inflammatory drugs (NSAIDs) clonixin, diclofenac, piroxicam, ketoprofen, meloxicam, and paracetamol induced antinociception after intraperitoneal or intrathecal administration in mice submitted to an acute thermal algesiometric test without inflammation (tail-flick). Antinociception was evaluated by the increase in reaction time difference (Delta latency), between readings obtained before and after the administration of drugs. The antinociception induced by doses of NSAIDs producing between 20% and 30% of the maximum possible effect (MPE) 30 min after intraperitoneal and 15 min after intrathecal injections was compared with the antinociception obtained after pretreatment with 1 mg/kg atropine ip, 30 min before. Systemic atropine (1 mg/kg) significantly antagonized NSAID-induced antinociception in all cases, both after intraperitoneal and intrathecal administration. Cholinergic depletion by intracerebroventricular hemicholinium-3 (HC-3, 5 microg) 5 h before prevented the antinociceptive effect of all NSAIDs. These observations suggest that intrinsic muscarinic cholinergic facilitatory pathways represent an important modulating system in pain perception in this animal model of acute thermal pain. The results of the present work support the increasingly accepted notion that NSAIDs are effective analgesics even when inflammation is not present, acting by mechanisms that involve actions on spinal and supraspinal nociceptive transmission. It is suggested that, similar to morphine and clonidine, the active mechanism of NSAIDs may involve the release of acetylcholine (ACh) in the spinal cord.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Atropina/farmacologia , Medição da Dor/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Medição da Dor/métodos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
The inhibition of cyclooxygenase enzymes by nonsteroidal anti-inflammatory drugs (NSAIDs) does not completely explain the antinociceptive efficacy of these agents. It is known that cholinergic agonists are antinociceptive, and this study evaluates the interactions between carbachol and some NSAIDs. Antinociceptive activity was evaluated in mice by the acetic acid writhing test. Dose-response curves were constructed for NSAIDs and carbachol, administered either intraperitoneally (i.p.) or intrathecally (i.t.). The interactions of carbachol with NSAIDs were evaluated by isobolographic analysis after the simultaneous administration of fixed proportions of carbachol with each NSAID. All of the drugs were more potent after spinal than after systemic administration. The combinations of NSAIDs and carbachol administered i.p. were supra-additive; however, the i.t. combinations were only additive. Isobolographic analysis of the coadministration of NSAIDs and carbachol and the fact that atropine antagonized the synergistic effect suggest that carbachol may strongly modulate the antinociceptive activity of NSAIDs; thus, central cholinergic modulation would be an additional mechanism for the antinociceptive action of NSAIDs, unrelated to prostaglandin biosynthesis inhibition.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carbacol/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Carbacol/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Sinergismo Farmacológico , CamundongosRESUMO
UNLABELLED: We evaluated the noradrenergic modulation of the antinociceptive activity of diclofenac in mice using the acetic acid writhing test. Dose-response curves were obtained for the antinociceptive effect of diclofenac, phenylephrine, clonidine, desipramine, prazosin, and yohimbine administered both systemically and intrathecally, and ED(50)s were calculated. Noradrenergic modulation was evaluated by performing an isobolographic analysis of the systemic or intrathecal coadministration of fixed-ratio combinations of diclofenac with each adrenergic drug. The systemic, but not the intrathecal, combinations of diclofenac with phenylephrine or clonidine showed supraadditivity, suggesting that the activation of alpha(1) and alpha(2) adrenoceptors interfered with the nociceptive transmission at spinal and supraspinal levels. Supraadditive effects were not demonstrated for the intrathecal injection of diclofenac combined with phenylephrine, clonidine and a selective norepinephrine uptake inhibitor (desipramine) or adrenergic antagonists. We conclude that interaction between adrenoceptors and diclofenac can modulate antinociception by activating common or different mechanisms. Diclofenac has an antinociceptive activity that, in addition to cyclooxygenase inhibition, can be modulated by additive and supraadditive interactions with adrenergic drugs. IMPLICATIONS: Diclofenac analgesia in mice can be modulated by interaction with adrenergic drugs. The systemic but not the intrathecal administration of phenylephrine and clonidine produced supraadditive interactions. For desipramine, prazosin, and yohimbine, supraadditive interactions were not statistically demonstrated. The coadministration of drugs inducing supraadditive effects could be clinically relevant for the treatment of chronic pain because of reduction of doses and side effects.
Assuntos
Adrenérgicos/farmacologia , Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Diclofenaco/farmacologia , Animais , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Camundongos , Fenilefrina/farmacologia , Prazosina/farmacologia , Ioimbina/farmacologiaRESUMO
The frequency of oestrus cycles in female mice was significantly reduced by the implantation of a pellet of subcutaneous ketoconazole (50 mg every 6 days). The effect was more pronounced after 22 days than after 13 days and it was probably related with the progressive reduction in steroid synthesis induced by the inhibition of key steroidogenic P450 cytochromes by the drug. In addition, the influence of ketoconazole on the incidence of seizures after the administration of intraperitoneal pentylenetetrazol was evaluated in female mice. Pentylenetetrazol produced a higher percentage of seizures during dioestrus than during oestrus. Pretreatment with ketoconazole significantly increased the percentage of animals with induced seizures in oestrus but not in dioestrus as compared to controls, probably through reduced progesterone levels. The reduced seizure threshold confirm the modulatory role exerted by progesterone on central nervous system excitability, and may be relevant in epileptic patients undergoing antifungal therapy.
Assuntos
Antifúngicos/farmacologia , Ciclo Estral/efeitos dos fármacos , Cetoconazol/farmacologia , Convulsões/fisiopatologia , Animais , Convulsivantes/farmacologia , Feminino , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos , Pentilenotetrazol/farmacologia , Convulsões/induzido quimicamente , Fatores de TempoRESUMO
The antinociceptive activity of several nonsteroidal anti-inflammatory drugs (NSAIDs) that were administered either intraperitoneally or intrathecally was assessed in mice by two algesiometric tests. The first was the writhing test, which assessed the abdominal constrictions that were induced by intraperitoneal acetic acid (a chemical test), and the second was the tail flick test, which measured pain responses to heat stimuli. The corresponding effective doses and their relative potencies were compared because these tests use different nociceptive stimuli with different transmission pathways. The intraperitoneal and intrathecal dose-response curves for the antinociception induced by every NSAID that was tested were parallel in the writhing test. In the tail flick test, however, only the intraperitoneal and intrathecal dose-response curves for ketoprofen, piroxicam, naproxen, nimesulide, paracetamol and diclofenac were parallel. The results obtained in this study confirm that NSAIDs possess different abilities to induce inhibition of cyclooxygenase, and they can be indirectly assessed by their different antinociceptive activities, depending on the algesiometric assays that are used. The antinociception of most NSAIDs might involve central mechanisms. The findings demonstrate the increasing importance of the spinal cord in processing and modulating nociceptive input, because intrathecal administration of NSAIDs is always more effective (in terms of potency) than systemic administration; thus, the antinociceptive efficacy of NSAIDs strongly depends on the algesiometric assay that is used and on the type of the nociceptive stimulus to which the test subject is exposed.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medição da Dor/métodos , Limiar da Dor/efeitos dos fármacos , Animais , Comportamento Animal , Relação Dose-Resposta a Droga , Temperatura Alta , Injeções Intraperitoneais , Injeções Espinhais , Camundongos , Camundongos Endogâmicos , Nociceptores/efeitos dos fármacos , CaudaRESUMO
The influence of progesterone and oestrogens on the benzodiazepine withdrawal syndrome in mice was studied. The intraperitoneal administration of 15 mg/kg of flumazenil induced a withdrawal syndrome in chronic diazepam-treated mice, characterized by jerks, usually accompanied by tail lifts, and seizures. The principal finding of the present work is that the intensity of diazepam withdrawal syndrome was significantly reduced by acute administration of progesterone as revealed by a low incidence of jerks and seizures. The action of progesterone could be due to a modulatory role of the hormone on neuronal activity as an anxiolytic agent. The modulatory activity of progesterone appears to be related to changes in the pharmacological properties of benzodiazepine receptors.
Assuntos
Ansiolíticos/efeitos adversos , Diazepam/efeitos adversos , Moduladores GABAérgicos/efeitos adversos , Progesterona/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Animais , Estradiol/farmacologia , Estro , Feminino , Flumazenil , CamundongosRESUMO
1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Clonidina/farmacologia , Medição da Dor/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Clonidina/antagonistas & inibidores , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Injeções Intraventriculares , Camundongos , Naloxona/farmacologia , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Prazosina/análogos & derivados , Prazosina/farmacologia , Receptores Opioides/fisiologia , Ioimbina/farmacologiaRESUMO
The role of para-chlorophenylalanine and alpha-methyl-DL-p-tyrosine in the antinociceptive effects of the intracerebroventricular administration of the antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was studied using the acetic acid writhing test in mice. The results demonstrated an antinociceptive effect for all these antidepressants. Pretreatment with para-chlorophenylalanine significantly reduced the antinociception induced by the ED50's of imipramine and maprotiline, and did not modify the effects of zimelidine and clomipramine, pretreatment with alpha-methyl-tyrosine did not modify the antinociception induced by these drugs except maprotiline. Pretreatment with para-chlorophenylalanine plus alpha-methyltyrosine significantly reduced the antinociceptive effect of all the antidepressants tested. The main finding of the present study is that the association of para-chlorophenylalanine plus alpha-methyltyrosine reduced the antinociceptive action of all the antidepressants. This means that critical levels of both 5-HT and NA are responsible for mediating the antinociceptive effects of antidepressants on the writhing test in mice.
Assuntos
Analgesia , Antidepressivos/farmacologia , Fenclonina/farmacologia , Metiltirosinas/farmacologia , Serotoninérgicos/farmacologia , Acetatos/administração & dosagem , Acetatos/intoxicação , Ácido Acético , Animais , Clomipramina/farmacologia , Interações Medicamentosas , Fenclonina/administração & dosagem , Imipramina/farmacologia , Injeções Intraventriculares , Maprotilina/administração & dosagem , Maprotilina/farmacologia , Metiltirosinas/administração & dosagem , Camundongos , Norepinefrina/metabolismo , Distribuição Aleatória , Serotonina/metabolismo , Serotoninérgicos/administração & dosagem , Zimeldina/farmacologia , alfa-MetiltirosinaRESUMO
This study represents the first investigation demonstrating the contractile response to exogenous acetylcholine (ACh) in the isolated human vas deferens. Pharmacological characterization of cholinergic receptors was achieved using selective antagonists to define receptor subtypes. In the HVD the effect of exogenous ACh is revealed as a dose-dependent sudden increase in the basal tension of the vasa. The ACh receptors of the HVD were competitively antagonized by atropine (ATR) with a high pA2 value (8.78). The main finding of this study is the presence of cholinergic receptors of the pharmacologically defined M1-ACh subtype in the isolated HVD, according to the pA2 values obtained with pirenzepine (PRZ) 7.39, AF-DX 116 (AF) 5.92 and 4-DAMP 5.65, M1-ACh, M2-ACh and M3-ACh selective antagonists, respectively. Prazosin (PZ), a selective alpha 1-adrenergic antagonist, displayed a similar competitive antagonism for the contractile response evoked both by ACh (pA2 = 8.69) and NE (pA2 = 8.58) in the HVD. The antagonism exerted by PZ on the ACh-induced contractile response of the HVD, suggests that ACh probably acts at a presynaptic level stimulating the release of NE from an adrenergic neuron. According to these findings, the receptor involved in this action, located in the proximity of the nerve terminals, seems to be of the M1-ACh subtype.
Assuntos
Receptores Muscarínicos/análise , Ducto Deferente/efeitos dos fármacos , Acetilcolina/farmacologia , Adulto , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Ducto Deferente/química , Ducto Deferente/fisiologiaRESUMO
1. Rat thoracic aortic rings with and without endothelium incubated in a Ca2(+)-free solution showed a significant reduction of the maximal contraction (E max) induced by norepinephrine (NE) and phenylephrine (Ph), while the contraction induced by a 70 mM KCl depolarizing solution was completely abolished. 2. After Ca2+ removal, pD2 values (-log ED50) for NE and Ph were significantly reduced only in vessels without endothelium. 3. Under control conditions, clonidine (C) induced a contraction only in vessels without endothelium; this response was completely abolished by Ca2+ removal and by nifedipine (10(-8) M). 4. Pre-incubation with nifedipine (10(-8) M) produced an effect similar, although less pronounced, than the removal of Ca2+ in vessels with and without endothelium. 5. Nevertheless, aortic rings with intact endothelium showed a greater reduction of E max than rings without endothelium, suggesting that the endothelial layer may act in synergism with calcium channel blockers to inhibit the contractions induced by alpha-adrenergic agonists. 6. The modulation exerted by the endothelium on alpha 1- and alpha 2-adrenergic-induced contractions in rat aortic rings seems to depend both on extracellular Ca2+ concentration and on the release and action of endothelial relaxing factor(s).
Assuntos
Cálcio/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Receptores Adrenérgicos alfa/fisiologia , Animais , Aorta Torácica/efeitos dos fármacos , Clonidina/farmacologia , Endotélio Vascular , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Nifedipino/farmacologia , Norepinefrina/farmacologia , Fenilefrina/farmacologia , Ratos , Receptores Adrenérgicos alfa/efeitos dos fármacosRESUMO
The effect of the intracerebral stimulation of the seventh cranial nerve was studied in anesthetized, artificially ventilated rats. The stimulation was carried out at the genu level by inserting a micropipette according to known stereotaxic coordinates. In 9 experiments, the cerebrospinal fluids pressure increased significantly 0.92 to 1.05 cm H2O above basal level after the stimulation of the same point on the left and right sides of the brain, without changes in mean arterial blood pressure. This response was interpreted as a sudden increase in cerebral blood volume produced by the dilatation of cerebral blood vessels. The section of the right greater superficial petrosal nerve abolished the increase in cerebrospinal fluid pressure after stimulation of the right side, while the response to stimulation of the left side was similar to the one observed in control animals. Consequently, the neurogenic vasodilation produced by intracerebral stimulation of the seventh cranial nerve in the rat seems to be mediated by a functional Chorobski-Penfield pathway running with the greater superficial petrosal nerve.
Assuntos
Pressão do Líquido Cefalorraquidiano/fisiologia , Nervo Facial/fisiologia , Animais , Estimulação Elétrica , Feminino , Masculino , Ratos , Ratos EndogâmicosRESUMO
The effets of the intracerebral stimulation of the seventh cranial nerve was studied in anesthetized, artificially ventilated rats, The stimulation was carried out at the genu level by inserting a micropipette according to known stereotaxic coordinates. In 9 experiments, the cerebrospinal fluids pressure increased significantly 0.92 to 1.05 cm H2O above basal level after the stimulation of the same point on the left and right sides of the brain, without changes in mean arterial blood pressure. This response was interpreted as a sudden increase in cerebral blood volume produced by the dilatation of cerebral blood vessels. The section of the right greater superficial petrosal nerve abolished the increase in cerebrospinal fluid pressure after stimulation of the right side, while the response to stimulation of the left side was similar to the one observed in control animals. Consequently, the neurogenic vasodilation produced by intracerebral stimulation of the seventh cranial nerve in the rat seems to be mediated by a functional Chorobski-Penfield pathway running with the greater superficial petrosal nerve