scholarly journals Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheralβ-Adrenoceptors

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Suk-Yun Kang ◽  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Ho-Jae Han ◽  
Alvin J. Beitz ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Formalin Test ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Bee Venom ◽  
Pain Models ◽  
Adrenergic Antagonists ◽  
Novel Strategy ◽  
Chronic Pain Conditions

The injection of diluted bee venom (DBV) into an acupoint has been used traditionally in eastern medicine to treat a variety of inflammatory chronic pain conditions. We have previously shown that DBV had a potent antinociceptive efficacy in several rodent pain models. However, the peripheral mechanisms underlying DBV-induced antinociception remain unclear. The present study was designed to investigate the role of peripheral epinephrine on the DBV-induced antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly enhanced the antinociceptive effect of DBV during the late phase of the formalin test, while chemical sympathectomy had no effect. Intraperitoneal injection of epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced antinociceptive effect. Moreover, injection of a phenylethanolamine N-methyltransferase (PNMT) inhibitor enhanced the DBV-induced antinociceptive effect. Administration of nonselectiveβ-adrenergic antagonists also significantly potentiated this DBV-induced antinociception, in a manner similar to adrenalectomy. These results demonstrate that the antinociceptive effect of DBV treatment can be significantly enhanced by modulation of adrenal medulla-derived epinephrine and this effect is mediated by peripheralβ-adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of peripheralβ-adrenoceptors could be a potentially novel strategy for the management of inflammatory pain.

scholarly journals Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
Author(s):  
Keshab Raj Paudel ◽  
SK Bhattacharya ◽  
GP Rauniar ◽  
BP Das
Keyword(s):  
Pain Perception ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Experimental Pain ◽  
Mechanical Hyperalgesia ◽  
Tail Flick ◽  
Hot Plate ◽  
Analgesic Effects ◽  
Pain Models ◽  
Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

scholarly journals Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey?

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nana Tsiklauri ◽  
Ivliane Nozadze ◽  
Gulnazi Gurtskaia ◽  
Merab G. Tsagareli
Keyword(s):  
Dorsal Hippocampus ◽  
Antinociceptive Effect ◽  
Male Rats ◽  
Opioid Antagonist ◽  
Tail Flick ◽  
Pain Models ◽  
Inflammatory Drugs ◽  
Antinociceptive Tolerance ◽  
Undesirable Feature

Emotional distress is the most undesirable feature of painful experience. Numerous studies have demonstrated the important role of the limbic system in the affective-motivational component of pain. The purpose of this paper was to examine whether microinjection of nonsteroidal anti-inflammatory drugs (NSAIDs), Clodifen, Ketorolac, and Xefocam, into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) tests compared to controls treated with saline into the DH. Subsequent tests on consecutive three days, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and posttreatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our data indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

Local antinociceptive action of fluoxetine in the rat formalin assay: role of l-arginine/nitric oxide/cGMP/KATP channel pathway

2018 ◽  
Vol 96 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Behnam Ghorbanzadeh ◽  
Mohammad Taghi Mansouri ◽  
Bahareh Naghizadeh ◽  
Soheila Alboghobeish
Keyword(s):  
Methylene Blue ◽  
Sodium Nitroprusside ◽  
Katp Channel ◽  
Formalin Test ◽  
Late Phase ◽  
Contrast Administration ◽  
Pre Treatment ◽  
Underlying Mechanisms ◽  
Peripheral Action

The present study was conducted to evaluate the local antinociceptive actions of fluoxetine, a selective serotonin reuptake inhibitor, and the possible involvement of the l-arginine/NO/cGMP/KATP channel pathway in this effect using the formalin test in rats. To elucidate the underlying mechanisms, animals were pre-treated with l-NAME, aminoguanidine, methylene blue, glibenclamide, l-arginine, sodium nitroprusside, or diazoxide. Local ipsilateral, but not contralateral, administration of fluoxetine (10–300 μg/paw) dose-dependently suppressed flinching number during both early and late phases of the test, and this was comparable with morphine also given peripherally. Pre-treatment with l-NAME, aminoguanidine, methylene blue, or glibenclamide dose-dependently prevented fluoxetine (100 μg/paw)-induced antinociception in the late phase. In contrast, administration of l-arginine, sodium nitroprusside, and diazoxide significantly enhanced the antinociception caused by fluoxetine in the late phase of the test. However, these treatments had no significant effect on the antinociceptive response of fluoxetine in the early phase of the formalin test. Our data demonstrate that local peripheral antinociception of fluoxetine during the late phase of the formalin test could be due to activation of l-arginine/NO/cGMP/KATP channel pathway. The peripheral action of fluoxetine raises the possibility that topical application of this drug (e.g., as a cream, ointment, or jelly) may be a useful method for relieving the inflammatory pain states.

Pharmacologic Interaction between Cannabinoid and either Clonidine or Neostigmine in the Rat Formalin Test

2003 ◽  
Vol 99 (3) ◽  
pp. 701-707 ◽  
Author(s):  
Myung Ha Yoon ◽  
Jeong Il Choi
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Formalin Test ◽  
Cannabinoid Receptor ◽  
Phase 1 ◽  
Antinociceptive Effect ◽  
Spinal Level ◽  
Isobolographic Analysis ◽  
Cannabinoid 1 Receptor

Background Although spinal cannabinoid receptor agonist (WIN 55,212-2) has been shown to encounter various models of pain, the role of two subtypes of cannabinoid receptor for the antinociceptive effect of cannabinoids has not been investigated at the spinal level. Spinal alpha 2 receptor agonist (clonidine) and cholinesterase inhibitor (neostigmine) are also active in the modulation of nociception. The authors examined the properties of drug interaction after coadministration of WIN 55,212-2-clonidine, and intrathecal WIN 55,212-2-neostigmine, and further clarified the role of cannabinoid 1 and 2 receptors in cannabinoid-induced antinociception at the spinal level. Methods Catheters were inserted into the intrathecal space of male Sprague-Dawley rats, and 50 microl of 5% formalin solution was injected into the hind paw to evoke the pain. Isobolographic analysis was used for evaluation of pharmacologic interaction. Results Intrathecal 55,212-2, clonidine, and neostigmine dose-dependently suppressed the flinching observed during phase 1 and 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of WIN 55,212-2-clonidine or WIN 55,212-2-neostigmine mixture in both phases. The antinociceptive effect of WIN 55,212-2 was antagonized by cannabinoid 1 receptor antagonist (AM 251) but not by cannabinoid 2 receptor antagonist (AM 630). No antinociceptive effect was seen after intrathecal administration of cannabinoid 2 receptor agonist (JWH 133). Conclusions Intrathecal 55,212-2, clonidine, and neostigmine attenuate the facilitated state and acute pain. WIN 55,212-2 interacts synergistically with either clonidine or neostigmine. The antinociception of WIN 55,212-2 is mediated through the cannabinoid 1 receptor, but not the cannabinoid 2 receptor, at the spinal level.

Analgesic Effect of Electric Stimulation of Peripheral Nerves with Different Electric Frequencies Using the Formalin Test

2000 ◽  
Vol 28 (02) ◽  
pp. 291-299 ◽  
Author(s):  
Ching-Liang Hsieh ◽  
Chi-Chung Kuo ◽  
Yueh-Sheng Chen ◽  
Tsai-Chung Li ◽  
Ching-Tou Hsieh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Analgesic Effect ◽  
Early Phase ◽  
Electric Stimulation ◽  
Formalin Test ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Neck Muscle ◽  
Nociceptive Response ◽  
Nociceptive Responses

Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 μl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.

scholarly journals Spinal Noradrenergic Modulation and the Role of the Alpha-2 Receptor in the Antinociceptive Effect of Intrathecal Nefopam in the Formalin Test

2014 ◽  
Vol 27 (1) ◽  
pp. 23 ◽  
Author(s):  
Shin Ho Jeong ◽  
Bong Ha Heo ◽  
Sun Hong Park ◽  
Woong Mo Kim ◽  
Hyung Gon Lee ◽  
...  
Keyword(s):  
Formalin Test ◽  
Antinociceptive Effect ◽  
Noradrenergic Modulation

scholarly journals Comparative evaluation of phasic and chemical antinociceptive action of a conventional and a novel anticonvulsants in experimental models of tail flick and formalin test

2019 ◽  
Vol 7 (2) ◽  
pp. 323
Author(s):  
Saurabh Kansal ◽  
Rohan Sirohi ◽  
Ruchika Agarwal
Keyword(s):  
Analgesic Effect ◽  
Formalin Test ◽  
Opioid Analgesic ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Experimental Models ◽  
Phase Response ◽  
Tail Flick ◽  
Second Phase ◽  
Tail Flick Test

Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinician.Methods: This study determined the analgesic effect of gabapentin (a conventional anticonvulsant) and levitiracetam (a novel anticonvulsant) in rats in different types of acute and chronic nociceptive test like tail flick and formalin test and compared its potency with a conventional non opioid analgesic diclofenac.Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test but significantly suppressed the late phase response while levitiracetam produced no any type of significant effect in both phases. In tail flick test gabapentin as well as levitiracetam produced no any significant analgesic effect while diclofenac produced significant reduction of pain in tail flick test as well as in both phases of formalin test.Conclusions: Thus, we have observed that gabapentin produced antinociception in chronic pain as second phase of formalin test reflects chronic inflammatory pain while levitiracetam did not produce any type of antinociceptive effect as it could not suppress the pain significantly in both tail flick and formalin test. 

scholarly journals Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity

2020 ◽  
Vol 21 (24) ◽  
pp. 9685
Author(s):  
Marta Szandruk-Bender ◽  
Benita Wiatrak ◽  
Łukasz Szczukowski ◽  
Piotr Świątek ◽  
Maria Rutkowska ◽  
...  
Keyword(s):  
Formalin Test ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Tail Flick ◽  
High Dose ◽  
Nociceptive Response ◽  
Tail Flick Test ◽  
Oxadiazole Derivatives ◽  
High Doses ◽  
Derivatives Of

Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.

Alleviation of pain and depression by specific neural transplants: Fine structural correlates

1992 ◽  
Vol 50 (2) ◽  
pp. 1066-1067
Author(s):  
George D. Pappas ◽  
Jacqueline Sagen
Keyword(s):  
Opioid Peptides ◽  
Chromaffin Cells ◽  
Pain Sensitivity ◽  
Opioid Peptide ◽  
Local Source ◽  
Pain Models ◽  
Neural Transplants ◽  
Adrenergic Antagonists ◽  
Csf Levels ◽  
Donor Source

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.

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