Antinociception Induced by Moringa Stenopetela (Baker f.) Cufod. Leaves Extract and Possible Mechanisms of Action

Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.

Efeitos dos receptores adrenérgicos no reparo tecidual cutâneo / Effects of adrenergic receptors in cutaneous tissue repair

Os receptores adrenérgicos regulam diversas funções do sistema tegumentar; entretanto, o papel destes receptores no processo de reparo tecidual cutâneo ainda não é completamente compreendido. O objetivo deste trabalho foi investigar o papel dos receptores alfa- e beta-adrenérgicos no reparo tecidual cutâneo em ratos. Inicialmente observamos que o bloqueio dos receptores beta1- e beta2-adrenérgicos (através da administração de propranolol) reduz a contração, a re-epitelização e a deposição de colágeno em lesões excisionais cutâneas, mas aumenta o infiltrado inflamatório, a proliferação celular, a densidade miofibroblástica e de vasos sanguíneos. Em seguida avaliamos se ambos receptores beta1- e beta2-adrenérgicos participam das alterações causadas pela administração de propranolol no reparo de lesões excisionais cutâneas e se os receptores alfa1- e alfa2-adrenérgicos participam do reparo destas lesões. O bloqueio de ambos receptores beta1- e beta1-adrenérgicos retarda a resposta inflamatória, o desenvolvimento do tecido de granulação e o remodelamento do tecido. Entretanto, o bloqueio do receptor beta1-adrenérgico não altera a re-epitelização. Além disso, o bloqueio dos receptores alfa1- e alfa2-adrenérgicos não compromete o reparo de lesões excisionais cutâneas. Posteriormente investigamos se o retardo induzido pela administração de propranolol no reparo tecidual cutâneo ocorre através da ativação dos receptores alfa-adrenérgicos. O bloqueio simultâneo dos receptores beta1-, beta2-, alfa1- e alfa2-adrenérgicos prejudica o fechamento, a re-epitelização, a mobilização de mastócitos e a proliferação celular de lesões excisionais cutâneas sem um efeito sinérgico ou a ativação dos receptores a-adrenérgicos. Além disso, estudamos os efeitos dos receptores alfa- e beta-adrenérgicos na formação do tecido de granulação em implantes de esponjas de poliuretano. O bloqueio dos receptores beta1- e beta2-adrenérgicos, mas não o bloqueio dos receptores alfa1 e alfa2...

Adrenoceptors regulate several functions of the skin; however, the role of adrenoceptors on cutaneous wound healing is not completely understood yet. The aim of this study was to investigate the role of the alfa- and beta-adrenoceptors on cutaneous wound healing in rats. Firstly, we observe that the blockage of beta1- and beta2-adrenoceptors (through propranolol administration) reduces wound contraction, re-epithelialization, and collagen deposition, but increases inflammatory infiltrate, cellular proliferation, density of myofibroblasts and blood vessels. Subsequently, we evaluate if both beta1- and beta2-adrenoceptors play a role in the propranolol-induced alterations on cutaneous wound healing and if alfa1- and alfa2-adrenoceptors participate in cutaneous wound healing. The blockade of both beta1- e beta2-adrenoceptors delays inflammatory response, granulation tissue formation and tissue remodeling. However, the blockade of beta1-adrenoceptors does not alter re-epithelialization. Moreover, the blockage of the alfa1- and alfa2-adrenoceptors does not compromise tissue repair of the cutaneous excisional lesions. Furthermore, we evaluate if propranolol-induced alterations on cutaneous wound healing occur through alfa1- and alfa2-adrenoceptors activation. The simultaneous blockade of beta1-, beta2-, alfa1- and alfa2-adrenoceptors impairs wound contraction, re-epithelialization, mast cells mobilization, and cellular proliferation of the cutaneous excisional lesions without a synergic effect or alfa-adrenoceptors activation. In addition, we study the effects of alfa- and beta-adrenoceptors blockade on granulation tissue formation in polyurethane sponges implants. The blockade of beta1- and beta2-adrenoceptors, but not alfa1- and alfa2-adrenoceptors, delays inflammatory cells migration, myofibroblastic differentiation, angiogenesis, and collagen fibers organization. Moreover, we also evaluate the effects of administration of a low dose of propranolol ...

Locus coeruleus modulates thalamic nociceptive responses via adrenoceptors.

This study investigated the parafascicular (PF) neuronal nociceptive responses and their modulation following electrical stimulation of the locus coeruleus (LC) and intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of two alpha-adrenoceptor antagonists, the alpha2-antagonist, yohimbine, and the alpha1-antagonist, prazosin. The main results were as follows: (1) the nociceptive evoked discharges in PF neurons were suppressed by preceding stimulation of LC; (2) the suppressive effect of LC stimulation on PF neurons was replaced by a facilitatory effect following pretreatment of i.t. yohimbine in 14 units tested, while i.t. prazosin failed to alter the LC-induced suppression, even when the prazosin dose was doubled; (3) i.c.v. pretreatment with prazosin strengthened the suppressive effect of LC stimulation on PF neurons; (4) i.c.v. norepinephrine (NE) administration induced, in PF neurons, a biphasic response to noxious stimulation; an early, brief (about 10 min) inhibitory effect followed by a late, long-lasting facilitatory effect; and (5) i.c.v. pretreatment of yohimbine or prazosin prevented the inhibitory or facilitatory responses released by NE, respectively. These results provide evidence that: (1) the LC-descending projections exhibit a suppressive effect on nociceptive transmission at the spinal level through alpha2-receptors; and (2) the LC-ascending projections exhibit dual effects, facilitatory and inhibitory, at the medial thalamus (PF) level through alpha1- and alpha2-receptors, respectively.

Cardiac B-receptors in experimental Chagas`disease

Estudaram-se os receptores beta cardiacos de camundongos infectados pelo Trypanosoma cruzi na fase pos-aguda da doenca de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anomalas as catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcacao dos receptores beta cardiacos dos camundongos normais e dos infectados na fase pos-aguda (45 a 90 dias pos-infeccao). O numero dos sitios de fixacao foi similar nos dois grupos, 78.591 ñ 3.125 fmol/mg. Proteina no grupo controle. Em vez disso, a afinidade verificou-se significamente diminuida no grupo chagasico (Kd = 7.299 ñ 0.212 nM) p < 0.001. Os resultados obtidos demonstraram que as modificacoes observadas na estimulacao adrenergica do miocardio chagasico se correlacionam com a menor afinidade dos receptores beta cardiacos e que estas alteracoes exerceriam uma parte determinante para as consequencias funcionais que sao detectadas na fase cronica.