Abstract

 Introduction: Hyperalgesia is considered as one the marked signs of subchronic diabetes mellitus that could affect the life style of the patients. With c onsidering the potential anti-diabetic effect of the medicinal plant Withania somnifera (WS)( ashwagandha), this study was designed to investigate the analgesic effect of WS on formalin-induced nociceptive responses (standard formalin test) in diabetic rats.

Methods: Rats were divided into control, WS-treated control, diabetic, sodium salicylate (SS)-treated control and diabetic and WS-treated diabetic groups. For induction of diabetes, streptozotocin (STZ) was used at a single dose. The treatment groups received oral administration of ashwagandha -mixed rat pellet (6.25%) for two months.

 Results: The results showed that diabetic rats exhibited a higher score of pain at both phases of the formalin test and WS-treated diabetic rats exhibited a lower nociceptive score at both phases of the test (p<0.05). Meanwhile, SS administration significantly reduced pain score only at chronic phase of the test in the diabetic group (p<0.01).

  Discussion: Taken together, these results indicate that two-month administration of ashwagandha could attenuate nociceptive score in an experimental model of diabetes mellitus and this may be considered as a potential treatment for painful diabetic neuropathy.

A B S T R A C T

Introduction: The nucleus cuneiformis (NCF) and ventrolateral periaqueductal gray (vlPAG), two adjacent areas, mediate the central pain modulation and project to the nucleus raphe magnus (NRM).

 Methods: This study examined whether the antinociceptive effect of morphine microinjected into the NCF is influenced by inactivation of vlPAG and NRM in rats. Animals were bilaterally microinjected with morphine (2.5 µg/0.3 µl saline) into the NCF. Electrolytic lesions were made in vlPAG (0.1 mA, 45 sec) and/or NRM (1 mA, 30 sec). Tail-flick latency (TFL) was measured at 30, 60, 90 and 120 min after microinjection.

 Results: The results showed that TFLs are significantly decreased in vlPAG+NRM lesions group at 30 (P<0.001) and 60 (P<0.01) min after intra- NCF administration of morphine whereas TFLs did not affect in solely vlPAG lesion animals. Our findings show that concurrent lesions of NRM and vlPAG completely reversed the analgesic effect of morphine in NCF. However, vlPAG do not play a critical role directly in pain modulatory system elicited from NCF, at least at the level of morphine-induced analgesia.

 Discussion: It can be concluded that its interactive effect in descending pain modulation from NCF to NRM should not be neglected.

Introduction: Inflammatory pain is a common sign of chronic diseases. Some brain regions such as locus coeruleus (LC) of the brainstem nor-epinephrine (NE) system have a key role in The mechanisms of the pain modulation and dependence. Bupropion synthesized as an antidepressant, but it is using for smoke cessation. It can change morphine withdrawal signs such as pain related behaviors. This study tested the acute effect of intra-LC microinfusion of bupropion on the formalin-induced pain behavior in rats. 

Introduction: Beside its autonomic functions, the nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. 17β-Estradiol is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi microinjection of 17β-estradiol can elicit the analgesic responses. 17β-Estradiol modulates nociception by binding to estrogenic receptors as well as allosteric interaction with other membrane-bound receptors like GABAA receptors. This study aimed to examine the role of GABAA receptors in the pain modulating effect of intra-LPGi injection of 17β-estradiol.
Methods: To study the antinociceptive effects of 17β-estradiol, cannulation into the LPGi nucleus of male Wistar rats was performed. About 500 nL of drug was administered 15 minutes prior to formalin injection (50 μL of 4%). Then, formalin-induced flexing and licking behaviors were recorded for 60 minutes. For evaluating the role of GABAA receptors in the estradiol-induced pain modulation, 17β-estradiol was administered into the LPGi nucleus 15 minutes after the injection of 25 ng/μL bicuculline (the GABAA receptor antagonist). Then, the formalin-induced responses were recorded.
Results: The results of the current study showed that intra-LPGi injection of 17β-estradiol decreased the flexing duration in both phases of formalin test (P<0.001); but it only attenuated the second phase of licking behavior (P<0.001). 17β-estradiol attenuated the second phase of formalin test of both behaviors (P<0.001). Bicuculline prevented the antinociceptive effect
of intra-LPGi 17β-estradiol in both first and second phases of formalin-induced responses (P<0.001).
Conclusion: According to the results of this study, the analgesic effect of intra-LPGi 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.