Avaliação dos efeitos da crotoxina isolada do veneno de serpente Crotalus durissus terrificus sobre a transecção do nervo ciático de ratos: avaliação histológica da formação do neuroma e capacidade de interferir com a condutividade nervosa (dor)

Pós-graduação em Medicina Veterinária - FMVZ

Efeitos determinados pela amitriptilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Serotonergic modulation in neuropathy induced by oxaliplatin: Effect on the 5HT(2C) receptor

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

Leg Amputation for an Extensive, Severe and Intractable Sickle Cell Anemia Ulcer in a Brazilian Patient

A 35-year-old African Brazilian patient had sickle cell anemia complicated with recurrent vasoocclusive (VOC) crises and refractory painful leg ulcers for 16 years. The ulcers started over both medial malleoli and expanded gradually. The ulcer on the left leg spread from the foot to the knee circumferentially and was refractory to all forms of therapy within the frame work of multi-disciplinary care. The patient agreed to a below the knee amputation of the left leg. He felt much better after the amputation but developed severe neuropathic phantom pain that was well controlled medically. He could differentiate the sickle cell anemia and ulcer pain from the neuropathic pain. About 6 months after the amputation he had dengue fever with fatal outcome. This is the first report of treatment of refractory sickle cell anemia leg ulcer with amputation and probably the first report of a Brazilian patient with sickle cell anemia and dengue fever.

Synaptic plasticity and sensory-motor improvennent following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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

Métodos de avaliação da eficácia dos tratamentos para a dor

Pain is a subjective condition and, thus, difficult to measure. The best tools to assess pain are the pain evaluation questionnaires, which provide either diagnostic, pain evolution or pain intensity information. To provide information which could help differentiate between nociceptive pain and neuropathic pain is one of the most important functions of these questionnaires. The questionnaires can measure pain intensity, quality of life, or sleep quality. Quality of life and sleep are two really important characteristics to assess the pain impact on patients' life. Pain intensity assessing questionnaires combine physical evaluations with questions, providing information either from the patient sensations or clinical assessment of pain manifestations as well as the underlying biological mechanisms (such as hyperalgesia or allodynia). For example, the Pain Detect questionnaire has two parts: the patient form (intuitive, with pictures and easy understandable) and the physician form. Thus, in this questionnaire, subjective information is provided by the patient and the objective one is provided by the physician. Other pain intensity questionnaires are NPSI, DN4, LANSS or StEP. Quality of life questionnaires are versatile (can be used in different pathologies). These questionnaires include functional self-evaluation questions, and other ones associated to physical and mental health. Two of such quality of life questionnaires are SF-36 and NHP. Sleep evaluation questionnaires include quantitative features such as the number of sleep interruptions, sleep latency or sleep duration as well as qualitative characteristics such as rest sensation, mood and dreams. One of the most used sleep evaluation questionnaires is PSQI, which includes patient questions and bed-partner questions, providing information from two points of view.

Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain

Cancer pain is an important clinical problem and may not respond satisfactorily to the current analgesic therapy. We have characterized a novel and potent analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in a rat model of cancer pain induced by intraplantar injection of Walker 256 carcinoma cells. Intraplantar injection of tumor cells caused the development of hyperalgesia and allodynia, detected on day 5 after tumor cell inoculation. Crotalphine (6 μg/kg), administered p.o., blocked both phenomena. The antinociceptive effect was detected 1 h after treatment and lasted for up to 48 h. Intraplantar injection of nor-binaltorphimine (50 g/paw), a selective antagonist of κ-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10 μg/paw), a selective antagonist of δ-opioid receptors, partially reversed this effect. On the other hand, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP, 20 g/paw), an antagonist of μ-opioid receptors, did not modify crotalphine-induced antinociception. These data indicate that crotalphine induces a potent and long lasting opioid-mediated antinociception in cancer pain. © 2013 Elsevier Inc.

Increased susceptibility to development of anhedonia in rats with chronic peripheral nerve injury: Involvement of sleep deprivation?

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

Diabetic peripheral neuropathy in ankles and feet: muscle strength and plantar pressure

This study aims to evaluate and correlate the vascular, sensory and motor components related to the plantar surface in individuals with diabetic peripheral neuropathy. 68 patients were categorized into two groups: 28 in the neuropathic group and 40 in the control group. In each patient, we assessed: circulation and peripheral perfusion of the lower limbs; somatosensory sensitivity; ankle muscle strength; and pressure on the plantar surface in static, dynamic and gait states. We used the Mann-Whitney test and analysis of variance (ANOVA and MANOVA) for comparison between groups, and performed Pearson and Spearman linear correlations amongst the variables (P < 0.05). The somatosensory sensitivity, peripheral circulation and ankle muscle strength were reduced in the neuropathic group. In full peak plantar pressures, no differences were seen between groups, but differences did appear when the foot surface was divided into regions (forefoot, midfoot and hindfoot). In the static condition, the plantar surface area was greater in the neuropathic group. In the dynamic state, peak pressures in the neuropathic group, were higher in the forefoot and lower in the hindfoot, as well as lower in the hindfoot during gait. There were positive or negative correlations between the sensitivity deficit, dorsal ankle flexor strength, plantar surface area, and peak pressure by plantar region. The sensitivity deficit contributed to the increased plantar surface area.