Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats.

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating oral GBP treatment (30, 60, 120 mg/kg, 60 min prior to chronic constriction of the sciatic nerve (CCSN) along 15-day treatment post-injury, 12 h/12 h) by monitoring spontaneous and induced-pain behaviors in Wistar rats on 5th and 15th days post-injury during early neuropathic events. CCSN animals receiving saline were used as controls. Another aim of this study was to evaluate GBP effects on myelin basic protein (MBP) on the 5th and 15th days post-injury and nerve morphology by transmission electron microscopy to address nerve regeneration. On the 5th and 15th days, GBP (60 mg/kg) reduced neuropathic pain behaviors (scratching and biting) in the ipsilateral paw and alleviated mechanical allodynia in comparison with the neuropathic saline group. GBP significantly increased climbing and rearing behaviors in CCSN and CCSN-free animals suggesting increased motor activity rather than sedation. We found three-fold significant increase in MBP expression by western blots on the 15th day when compared to controls. In addition, GPB (60 mg/kg) improved nerve axonal, fiber and myelin area 15 days post-surgery. In conclusion, GBP alleviated mechanical and thermal allodynia and spontaneous pain-related behaviors and improved later nerve morphology. Our findings suggest that GBP improve nerve remyelination after chronic constriction of the sciatic nerve.

Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats.

Oral gabapentin treatment accentuates nerve and peripheral inflammatory responses following experimental nerve constriction in Wistar rats.

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating whether oral GBP treatment could improve nerve inflammation response after sciatic nerve constriction in association with selected pain and motor spontaneous behavior assessments in Wistar rats. We evaluated nerve myeloperoxidase (MPO) and inflammatory cytokines on the 5th day post-injury, time in which nerve inflammation is ongoing. In addition, the role of GBP on carrageenan-induced paw edema and peritoneal cell migration was analyzed. GBP was given by gavage at doses of 30, 60 and 120mg/kg, 60min prior to chronic constriction of the sciatic nerve (CCSN) and during 5 days post-injury, 12/12h. CCSN animals treated with saline were used as controls and for behavioral and inflammation assessments untreated sham-operated rats were also used. On the 5th day, GBP (60 and 120mg/kg) alleviated heat-induced hyperalgesia and significantly increased delta walking scores in CCSN animals, the latter suggesting excitatory effects rather than sedation. GBP (60mg/kg) significantly increased nerve MPO, TNF-α, and IL-1ß levels, comparing with the saline group. GBP (120mg/kg) reduced the anti-inflammatory cytokine IL-10 nerve levels compared with the CCSN saline group. Furthermore, GBP (60 and 120mg/kg) increased carrageenan-induced paw edema and peritoneal macrophage migration compared with the CCSN saline group. Altogether our findings suggest that GBP accentuates nerve and peripheral inflammatory response, however confirmed its analgesic effect likely due to an independent CNS-mediated mechanism, and raise some concerns about potential GBP inflammatory side effects in widespread clinical use.

Pain in tropical spastic paraparesis/HTLV-I associated myelopathy patients.

OBJECTIVE: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (TSP/HAM) is a chronic myelopathy, and pain has been mentioned as a frequent sensory symptom in this condition. The authors aimed at analyzing this symptom in a TSP/HAM patients series. METHOD: For this, 46 patients were analyzed considering demographic and clinical characteristics and complaint of pain as to verbal description, time of onset and classification, correlated with the degree of motor disability and type of pain. RESULTS: Among the 46 TSP/HAM patients, 28 (60.8%) complained of pain, predominant in the early phase of the disease. Most of the patients exhibited neuropathic characteristics of pain, correlated with increased motor disability. CONCLUSION: Pain in TSP/HAM patients is a frequent and early symptom, and the neuropathic type is predominant (57.1%) and paralleled with increased incapacitation. The pathogenic involvement of cytokines may possibly be involved in the meaning of this symptom in this condition.

Pain in tropical spastic paraparesis/HTLV-I associated myelopathy patients / Dor em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV-I

OBJECTIVE: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (TSP/HAM) is a chronic myelopathy, and pain has been mentioned as a frequent sensory symptom in this condition. The authors aimed at analyzing this symptom in a TSP/HAM patients series. METHOD: For this, 46 patients were analyzed considering demographic and clinical characteristics and complaint of pain as to verbal description, time of onset and classification, correlated with the degree of motor disability and type of pain. RESULTS: Among the 46 TSP/HAM patients, 28 (60.8 percent) complained of pain, predominant in the early phase of the disease. Most of the patients exhibited neuropathic characteristics of pain, correlated with increased motor disability. CONCLUSION: Pain in TSP/HAM patients is a frequent and early symptom, and the neuropathic type is predominant (57.1 percent) and paralleled with increased incapacitation. The pathogenic involvement of cytokines may possibly be involved in the meaning of this symptom in this condition.

OBJETIVO: A Paraparesia Espástica Tropical/Mielopatia Associada ao HTLV-I (PET/MAH) é uma mielopatia crônica, e a dor tem sido mencionada como um sintoma sensitivo freqüente nessa condição. Os autores objetivam analisar esse sintoma numa série de pacientes com PET/MAH. MÉTODO: Para isso, 46 pacientes foram analisados considerando características demográficas e clínicas, e queixa de dor do ponto de vista da descrição verbal, tempo de início e classificação, correlacionados com o grau de incapacitação motora e o tipo de dor. RESULTADOS: Dentre os 46 pacientes com PET/MAH, 28 (60,8 por cento) se queixavam de dor, predominando na fase inicial da doença. A maioria dos pacientes evidenciou características de dor neuropática, correlacionada com aumento da incapacitação motora. CONCLUSÃO: A dor em pacientes com PET/MAH é um sintoma freqüente e inicial, sendo o tipo neuropático predominante (57,1 por cento) e em paralelo com maior incapacitação. O envolvimento patogênico das citocinas poderá possivelmente estar relacionado com o significado desse sintoma nessa condição clínica.

Antispasmodic effect of the essential oil of Plectranthus barbatus and some major constituents on the guinea-pig ileum.

The effects of the Plectranthus barbatus essential oil (PBEO) at concentrations ranging form 1 to 300 microg/mL and some major constituents, i. e., alpha-pinene, myrcene and caryophyllene in the ratio and amount found in the oil, were studied on the contractility of the guinea-pig ileum. PBEO decreased the basal tonus of the ileum with a maximal response (R (max); % of K (+)-contraction) of 62.7 +/- 3.8 % compared with 36.6 +/- 4.5 % inhibition achieved with alpha-pinene and 68 +/- 2.6 % with papaverine. The other constituents had only a slight effect. PBEO also blocked the phasic contractions evoked by acetylcholine with an R (max) of 85 +/- 3.6 % compared with 54.4 +/- 3.5 % inhibition induced by alpha-pinene and 12.4 +/- 5.6 % with caryophyllene. The contractions induced by histamine or barium chloride were also decreased in amplitude by PBEO with an R (max) of 94.3 +/- 5.7 % and 100 %, respectively. In addition, PBEO relaxed tissues pre-contracted with 60 mM K (+) with an R (max) of 89.7 +/- 2.7 % compared with 55.4 +/- 4.6 % relaxation induced by alpha-pinene. The other major constituents studied had no significant effect. Furthermore, at the higher concentration used, i. e., 300 microg/mL, PBEO decreased the maximal response of calcium chloride (10 ( - 7) to 10 ( - 3) M) induced contraction in depolarized tissues by 29.1 +/- 9.53 % (p < 0.05). In addition, the component of the contraction elicited by a single dose of carbachol (CCh; 100 microM) added on nifedipine (10 microM) treated tissues or at very low extracellular calcium concentration were blocked by PBEO (300 microg/mL) in 85.7 +/- 7.8 % (p < 0.05; n = 5) and 81.2 +/- 6.4 % (p < 0.05; n = 4), respectively. These data show that PBEO has intestinal relaxant and antispasmodic activity and suggest that this effect is not related to antagonism in extracellular receptors for neurotransmitters or autacoids and it seems to occur downstream of calcium entry or release from internal stores. The main active principle for its relaxant and spasmolytic activity seems to be alpha-pinene.