RESUMEN
Ontogenetic sexual dimorphism is observed in different primate species, with ecological and evolutionary relationships explaining this pattern. Understanding the growth of the southern brown howler monkey elucidates not only the ecology and evolution but also contributes to conservation projects for this species. Throughout 20 years of the Centro de Pesquisas Biológicas de Indaial-Projeto Bugio, Brazil, we collected morphological data on 105 howlers of the Alouatta guariba species to identify the growth differences between ontogenetic categories and sexes and generate a growth curve to estimate the age of rescued individuals. Linear measurements were employed to obtain body length as well as the dimensions of the head and limbs. All individuals were also weighed to obtain body mass. We assessed growth rate and duration using allometric analysis based on the individuals' ages. We compared growth rate and duration among infant, juvenile, and adult howlers and between sexes. We provide growth curves for body size for both sexes using the Von Bertalanffy model. Infants have accelerated growth rate in comparison to the juveniles and adults, with no differences between sexes in establishing body length at this ontogenetic stage. Males have a prolonged development duration from the juvenile stage, reaching adulthood later than females, which explains the body length differences found in this species. Variables of head and limbs analyzed also showed differences in growth rate and duration, but not so consistently among ontogenetic stages. Mass was not a good variable to understand the growth differences of the animals, since many arrived feeble in the project and may have lost mass due to different circumstances in old age. Therefore, growth curves were obtained only for body length, allowing the estimation of the age of these animals when rescued from the wild to more effectively provide needed care in captivity.
RESUMEN
Injury to peripheral nerves often results in a persistent neuropathic pain condition that is characterized by spontaneous pain, allodynia, and hyperalgesia. Nerve injury is accompanied by a local inflammatory reaction in which nerve-associated and immune cells release several pronociceptive mediators. Kinin B1 receptors are rarely expressed in nontraumatized tissues, but they can be expressed after tissue injury. Because B1 receptors mediate chronic inflammatory painful processes, we studied their participation in neuropathic pain using receptor gene-deleted mice. In the absence of neuropathy, we found no difference in the paw-withdrawal responses to thermal or mechanical stimulation between B1 receptor knock-out mice and 129/J wild-type mice. Partial ligation of the sciatic nerve in the wild-type mouse produced a profound and long-lasting decrease in thermal and mechanical thresholds in the paw ipsilateral to nerve lesion. Threshold changed neither in the sham-operated animals nor in the paw contralateral to lesion. Ablation of the gene for the B1 receptor resulted in a significant reduction in early stages of mechanical allodynia and thermal hyperalgesia. Furthermore, systemic treatment with the B1 selective receptor antagonist des-Arg9-[Leu8]-bradykinin reduced the established mechanical allodynia observed 7-28 d after nerve lesion in wild-type mice. Partial sciatic nerve ligation induced an upregulation in B1 receptor mRNA in ipsilateral paw, sciatic nerve, and spinal cord of wild-type mice. Together, kinin B1 receptor activation seems to be essential to neuropathic pain development, suggesting that an oral-selective B1 receptor antagonist might have therapeutic potential in the management of chronic pain.
Asunto(s)
Neuralgia/etiología , Receptor de Bradiquinina B1/deficiencia , Receptor de Bradiquinina B1/fisiología , Neuropatía Ciática/complicaciones , Animales , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Bradiquinina/uso terapéutico , Antagonistas del Receptor de Bradiquinina B1 , Femenino , Lateralidad Funcional , Expresión Génica/fisiología , Hiperalgesia/genética , Hiperalgesia/fisiopatología , Masculino , Ratones , Ratones Noqueados/fisiología , Neuralgia/terapia , Dimensión del Dolor/métodos , ARN Mensajero/metabolismo , Receptor de Bradiquinina B1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Piel/metabolismo , Piel/patología , Temperatura Cutánea/genética , Factores de TiempoRESUMEN
This study aimed to investigate further the mechanisms involved in the antinociception caused by dipyrone, given by intraperitoneal (i.p.) or intrathecal (i.t.) routes. The intraperitoneal administration of dipyrone to mice 30 min prior resulted in a significant and dose-related inhibition of the biting responses induced by i.t. injection of glutamate, trans-ACPD or substance P (SP). In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. Dipyrone, given either systemically (i.p.) or by i.t. route also caused a dose-dependent inhibition of phorbol myristate acetate (PMA)-induced nociception. Given by systemic route, dipyrone inhibited PMA-induced paw oedema formation. Collectively, these results extend previous data from our group indicating that glutamatergic-mediated pain responses, specifically those mediated by metabotropic receptor subtype, together with inhibition of neurokinin NK(1)-mediated response, account for the antinociceptive action of dipyrone in mice. Furthermore, we have also produced experimental evidence indicating that the activation of the protein kinase C-dependent pathway plays a role in the dipyrone antinociceptive action.
Asunto(s)
Dipirona/farmacología , Dimensión del Dolor/efectos de los fármacos , Proteína Quinasa C/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de Neuroquinina-1/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Activadores de Enzimas/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Masculino , Ratones , Dimensión del Dolor/métodos , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Neuroquinina-1/agonistas , Sustancia P/farmacologíaRESUMEN
This study sought to establish whether sensory neuropeptides and the capsaicin-sensitive fibres are involved in the nociception and oedema formation caused by intraplantar (i.pl.) injection of glutamate into the mouse paw. The i.pl. co-injection of the selective neurokinin (NK) NK(2) (SR 48968, 0.05-0.5 nmol/paw), and to a lesser extent the selective NK(1) (FK 888, 0.25-1.0 nmol/paw) receptor antagonists, resulted in a significant inhibition of glutamate-induced nociception. The percentages of inhibition were 82 and 37%, respectively. In contrast, the selective NK(3) receptor antagonist (SR 142801, 0.25-1.0 nmol/paw) failed to significantly affect glutamate-induced nociception. SR 48968, but not FK 888 or SR 142801, significantly inhibited (36%) glutamate-induced paw oedema formation. The i.pl. injection of kinin B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK (0.2-0.8 nmol/paw), but not the B(2) receptor antagonist HOE 140 (1.0-4.0 nmol/paw), together with glutamate, also inhibited glutamate-induced nociception (53%) in a graded manner, without affecting glutamate-induced paw oedema. The i.pl. co-injection of the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) (1 nmol/paw) failed to significantly inhibit glutamate-induced nociception or oedema. Finally, neonatal-capsaicin (50 mg/kg, s.c.) treatment inhibited glutamate-induced nociception by 69% and to a lesser extent glutamate-mediated oedema formation (30%). Collectively, the current results indicate that the nociception caused by i.pl. injection of glutamate in mice is clearly mediated by capsaicin-sensitive fibres and by release of neurokinins from sensory neurones that activate NK(2) receptors and to a lesser extent NK(1) receptors. Furthermore, kinins acting at B(1) (but not at B(2)) receptors also largely account for glutamate-mediated nociceptive behaviour response. In contrast, glutamate-induced paw oedema seems to be primarily mediated via activation of NK(2) receptors and stimulation of capsaicin-sensitive C-fibres. CGRP receptors do not seem to be involved in either of the glutamate responses.
Asunto(s)
Edema/fisiopatología , Ácido Glutámico/farmacología , Fibras Nerviosas/fisiología , Nociceptores/fisiología , Dolor/fisiopatología , Animales , Benzamidas/farmacología , Antagonistas de los Receptores de Bradiquinina , Péptido Relacionado con Gen de Calcitonina/metabolismo , Capsaicina/metabolismo , Capsaicina/farmacología , Dipéptidos/farmacología , Edema/inducido químicamente , Pie/fisiopatología , Indoles/farmacología , Masculino , Ratones , Fibras Nerviosas/efectos de los fármacos , Antagonistas del Receptor de Neuroquinina-1 , Nociceptores/efectos de los fármacos , Piperidinas/farmacología , Receptor de Bradiquinina B1 , Receptor de Bradiquinina B2 , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Receptores de Neuroquinina-1/efectos de los fármacos , Receptores de Neuroquinina-1/metabolismo , Receptores de Neuroquinina-2/antagonistas & inhibidores , Receptores de Neuroquinina-2/efectos de los fármacos , Receptores de Neuroquinina-2/metabolismoRESUMEN
This study characterizes the receptor subtypes and investigates some of the mechanisms by which glutamate, injected intraplantarly (i.pl.) into the mouse paw, produces nociception and paw oedema. I.pl. injection of glutamate induced a rapid-onset, dose-related pain response associated with oedema formation, with mean ED(50) values of 2.6 (1.6-4.3) and 0.5 (0.4-0.7) micromol/kg, respectively. Pretreatment with Chicago sky blue 6B (100 microg/kg), an inhibitor of glutamate uptake, caused a significant (about sixfold) reduction of the mean ED(50) value for glutamate-induced nociception, but not paw oedema. NMDA receptor antagonist MK 801, given by systemic (i.p.), intracerebroventricular (i.c.v.), i.pl. or intrathecal (i.t.) routes, produced graded inhibition of glutamate-induced nociception. Non-NMDA receptor antagonists NBQX or GAMS, metabotropic antagonist E4CPG, and also the antagonist that acts at the NMDA receptor-associated glycine binding site felbamate, significantly inhibited the nociception induced by glutamate. L(omega)-N-nitro-arginine (given i.p., i.t., i.pl. or i.c.v.) prevented the nociception and paw oedema caused by glutamate, an effect that was reversed by L-arginine but not by D-arginine. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), given i.pl., greatly potentiated glutamate-induced nociception and oedema formation. Finally, the i.pl. injection of glutamate was accompanied by a graded increase in the nitrite levels of the hindpaw exudate. It is concluded that the nociception caused by i.pl. injection of glutamate probably involves the activation of NMDA and non-NMDA receptors by a mechanism which largely depends on the activation of L-arginine-nitric oxide pathway. Glutamate-induced paw oedema seems to be primarily mediated by non-NMDA ionotropic glutamate receptors and release of nitric oxide.