Efeito do gliconato de cálcio e do fluoreto de fenilmetilsulfonil (PMSF) no tratamento da intoxicação aguda por organofosforado neuropático em galinhas, utilizando como protótipo do TRI-ORTO-CRESIL fosfato (TOCP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Enxerto venoso ao avesso e normal, com ou sem preenchimento de músculo, em regeneração nervosa de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Metabolismo glicídico em ratos submetidos à imobilização por desnervação do músculo esquelético

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Enxertos venosos ao avesso e normal, preenchidos com plasma rico em plaquetas em nervo misto de rato

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Citral: A monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A Catuama e o bilobalide na regeneração nervosa periférica de ratos submetidos à secção do nervo isquiático

The Catuama((R)) is composed of four Brazilian plants extracts (Paullinia cupana, Trichilia catigua, Ptychopetalum olacoides e Zingiber officinale). The Catuama((R)) is known as having neuroprotector, anti-inflammatory, antioxidant and antidepressant effects. Bilobalide, extracted from leaves of Ginkgo biloba, is known by its neuroprotective effect in the central and peripheral nervous systems. The present study evaluates the effect of Catuama((R)) and bilobalide on peripheral nerve regeneration in rats following a sciatic nerve section. Sciatic nerve of forty adult rats was transected with a 10-mm gap and the proximal and distal nerve stumps were fixed in a silicone tube filled with liquid collagen. The animals were divided into four groups: the control group (A), two groups treated with Catuama((R)) by gavage along 28 days after the surgery in different doses of 100 (B) and 400mg. kg(-1) (C) and the group using 200 mu M bilobalide (D) associated with the liquid collagen in the silicone tube. Evaluations were done by a walk test on the first, fifth and tenth week after the surgery. Electrophysiological stimulation and quantitative and qualitative histological analyses of the sciatic nerve and gastrocnemius muscle were also performed on the tenth week after the surgery. All groups showed good regeneration but no statistical difference was found between treatments and control groups (P > 0.05).

Investigação da participação de adrenoceptores α1 no efeito antinociceptivo da amitriptilina em um modelo de dor neuropática

Tricyclic antidepressants, such as amitriptyline, are inhibitors of serotonin and norepinephrine neuronal reuptake and this action has been implied in changes in pain threshold supporting its use to alleviate neuropathic pain. Although is known that 1 adrenoceptors participate in the antinociceptive effect of amitriptyline it is unclear which receptor subtype is the target for the increased synaptic levels of norepinephrine resultant from the inhibition of neuronal uptake. Paradoxically, several tricyclic antidepressants including amitriptyline also behave as antagonists of 1 adrenoceptors with different affinities for its subtypes: these drugs have 10 to 100-fold higher affinities for 1A than for 1B and 1D adrenoceptors. This work investigated the involvement of 1 adrenoceptors subtypes in the antinociceptive effect of the amitriptyline in a constriction of the sciatic nerve in rats by determining the effects of subtype selective 1 adrenoceptors antagonists. Fifteen days later, mechanical hyperalgesia was analyzed in a Randall-Selitto test. The 1A-selective antagonist RS100329 was the most potent antagonist of the contractions of the rat prostate, whereas the 1D-selective antagonist BMY 7378 (up to 100g/Kg) was unable to affect these contractions. The antagonist prazosin, BMY 7378 and 5-methyl urapidil inhibited the antinociceptive effect of the amitriptyline. However, the highly selective 1A adrenoceptor antagonist RS100329 was unable to affect the antinociception induced by amitriptyline. These results point out that 1B and/or 1D adrenoceptors, but not 1A, are involved in the antinociceptive effects of amitriptyline

Avaliação do efeito do citral na dor neuropática e na inflamação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos neuroprotetor e regenerativo do selante de fibrina derivado da peçonha de serpente combinado com células tronco mononucleares após reparo do nervo isquiático de ratos neonatos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite derived from leucine. The anti-catabolic effect of HMB is well documented but its effect upon skeletal muscle strength and fatigue is still uncertain. In the present study, male Wistar rats were supplemented with HMB (320 mg/kg per day) for 4 weeks. Placebo group received saline solution only. Muscle strength (twitch and tetanic force) and resistance to acute muscle fatigue of the gastrocnemius muscle were evaluated by direct electrical stimulation of the sciatic nerve. The content of ATP and glycogen in red and white portions of gastrocnemius muscle were also evaluated. The effect of HMB on citrate synthase (CS) activity was also investigated. Muscle tetanic force was increased by HMB supplementation. No change was observed in time to peak of contraction and relaxation time. Resistance to acute muscle fatigue during intense contractile activity was also improved after HMB supplementation. Glycogen content was increased in both white (by fivefold) and red (by fourfold) portions of gastrocnemius muscle. HMB supplementation also increased the ATP content in red (by twofold) and white (1.2-fold) portions of gastrocnemius muscle. CS activity was increased by twofold in red portion of gastrocnemius muscle. These results support the proposition that HMB supplementation have marked change in oxidative metabolism improving muscle strength generation and performance during intense contractions.

The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats

Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide-cyclic GMP pathway and of K+ channels. Crotalphine (0.2 or 5 mu g/kg, orally; 0.0006 mu g/paw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of delta-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of kappa-opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo[4,3-a]quinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive K+ channel blocker. The results suggest that peripheral delta-opioid and kappa-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain. Behavioural Pharmacology 23:14-24 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Neural mobilization reverses behavioral and cellular changes that characterize neuropathic pain in rats

Background: The neural mobilization technique is a noninvasive method that has proved clinically effective in reducing pain sensitivity and consequently in improving quality of life after neuropathic pain. The present study examined the effects of neural mobilization (NM) on pain sensitivity induced by chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted thereafter to 10 sessions of NM, each other day, starting 14 days after the CCI injury. Over the treatment period, animals were evaluated for nociception using behavioral tests, such as tests for allodynia and thermal and mechanical hyperalgesia. At the end of the sessions, the dorsal root ganglion (DRG) and spinal cord were analyzed using immunohistochemistry and Western blot assays for neural growth factor (NGF) and glial fibrillary acidic protein (GFAP). Results: The NM treatment induced an early reduction (from the second session) of the hyperalgesia and allodynia in CCI-injured rats, which persisted until the end of the treatment. On the other hand, only after the 4th session we observed a blockade of thermal sensitivity. Regarding cellular changes, we observed a decrease of GFAP and NGF expression after NM in the ipsilateral DRG (68% and 111%, respectively) and the decrease of only GFAP expression after NM in the lumbar spinal cord (L3-L6) (108%). Conclusions: These data provide evidence that NM treatment reverses pain symptoms in CCI-injured rats and suggest the involvement of glial cells and NGF in such an effect.

Plasma corticosterone levels in mouse models of pain

Background: Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs. Aims/Methods: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone. Results: Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice. Conclusion: Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.

Functional and morphometric differences between the early and delayed use of phototherapy in crushed median nerves of rats

This study evaluated the functional and quantitative differences between the early and delayed use of phototherapy in crushed median nerves. After a crush injury, low-level laser therapy (GaAs) was applied transcutaneously at the injury site, 3 min daily, with a frequency of five treatments per week for 2 weeks. In the early group, the first laser treatment started immediately after surgery, and in the delayed group, after 7 days. The grasping test was used for functional evaluation of the median nerve, before, 10, and 21 days after surgery, when the rats were killed. Three segments of the median nerve were analyzed histomorphometrically by light microscopy and computer analysis. The following features were observed: myelinated fiber and axon diameters, myelin sheath area, g-ratio, density and number of myelinated fibers, and area and number of capillaries. In the proximal segment (site of crush), the nerves of animals submitted to early and delayed treatment showed myelinated fiber diameter and myelin sheath area significantly larger compared to the untreated group. In the distal segment, the myelin sheath area was significantly smaller in the untreated animals compared to the delayed group. The untreated, early, and delayed groups presented a 50, 57, and 81% degree of functional recovery, respectively, at 21 days after injury, with a significant difference between the untreated and delayed groups. The results suggest that the nerves irradiated with low-power laser exhibit myelinated fibers of greater diameter and a better recovery of function.

Estimulação elétrica de alta voltagem em nervo ciático de ratos: estudo pelo IFC

OBJETIVO: Analisar a eficiência do tratamento com a estimulação elétrica de alta voltagem (EEAV) em três diferentes locais, aplicada precocemente na regeneração do nervo ciático submetido à lesão por esmagamento, e avaliada através do índice funcional do ciático (IFC), em ratos. MÉTODO: Após o esmagamento, 57 ratos foram submetidos à EEAV catódica nos parâmetros: frequência de 50Hz, 100V de tensão, 20 minutos diários, 5 dias por semana. Os ratos foram divididos aleatoriamente em: grupo controle; grupo gânglio; grupo gânglio + músculo; grupo músculo e; grupo simulado. O IFC foi avaliado semanalmente durante sete semanas, partindo do pré-operatório até a 6ª semana pós-operatória. RESULTADOS: Em comparação ao grupo controle, os resultados mostraram desempenho significativamente superior do grupo gânglio nas três primeiras semanas, e do grupo gânglio + músculo na 3ª semana, enquanto o grupo músculo teve desempenho significativamente negativo na 4ª e 6ª semanas. CONCLUSÃO: a EEAV aplicada precocemente, foi positiva no tratamento da região da medula e gânglio da raiz nervosa do ciático com o eletrodo dispersivo na região lombar contralateral ou no músculo gastrocnêmio. Porém, proporcionou efeitos negativos no tratamento com eletrodo ativo no músculo gastrocnêmio e dispersivo na coxa contralateral. Nível de evidência II, Estudo prospectivo comparativo.