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Background and objectives: Neuropathic pain is defined as pain caused by damage to the nerve as a result of a lesion or disease. It has been shown that ischemic preconditioning exerts a protective role in various tissue injuries; however, the effect of transplantation of remote ischemic preconditioning serum (RIPCs) on neuropathic pain symptoms has not been studied. The aim of this project is to investigate the effect of RIPCs transfusion by different routes of administration on neuropathic pain symptoms. Our secondary aim was to demonstrate the role of Schwann cells in the regeneration of sciatic nerve injury and to evaluate the change in the number of glial cells in the spinal cord dorsal horn. Methods: The sciatic nerve partial ligation method was used to induce neuropathic pain. Changes in neuropathic pain symptoms were assessed by measuring thermal hyperalgesia and mechanical allodynia. To determine the possible therapeutic site, alterations in the number of spinal cord lumbar posterior horn microglia and astrocytes were evaluated by ionized calcium-binding adapter molecule 1 (iba1) and glial fibrillary acidic protein (GFAP) immunostaining. Myelin basic protein immunohistochemistry was also used to assess Schwann cell immunoreactivity in the sciatic nerve. Results: In rats that underwent partial sciatic nerve ligation, neuropathic pain symptoms developed on average on day 12 and persisted up to day 21 (p

Background and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4+ and CD8+ T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8+ T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.

Introduction: For centuries, cannabinoids are known to be effective in pain relief. Itch is an unpleasant sensation that provokes a desire to scratch. Since itch and pain are two sensations sharing a lot in common, we aimed to investigate whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behavior and also observe whether modulation of nitric oxide (NO) production mediates the antipruritic effect of WIN 55,212-2. Methods: Scratching behavior is induced by intradermal injection of serotonin (50 µg/50 µL/mouse) to BALB/c mice. The cannabinoid agonist WIN 55,212-2 (1, 3, 10 mg/kg, IP) was given 30 min before serotonin injection. To observe the effect of NO modulation on the antipruritic effect of cannabinoids, the endothelial nitric oxide synthase (NOS) inhibitor L-NAME (3 mg/kg, IP), the neuronal NOS inhibitor 7-nitroindazole (3 mg/kg, IP), and the NO precursor L-arginine (100 mg/kg, IP) were administered together with WIN 55,212-2. Results: WIN 55,212-2 reduced serotonin-induced scratches at higher doses (3, 10 mg/kg; P

Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as "non-opioid analgesics" and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.

Amaç: Yakın zamanda parasetamol’ün anksiyolitik-benzeri etkileri olduğu ve bu etkilerine kannabinoid CB1 reseptörlerinin aracılık ettiği gösterilmiştir. Etkilerinde santral sinir sisteminin rolü olduğu uzun zamandır düşünülen ve etkileri açısından non-steroid anti-inflamatuvar ilaçlardan çok parasetamol ile benzerlik gösteren bir analjezik olan dipiron’un da antinosiseptif etkisinde kannabinoid sistemin rolü olduğu belirtilmiştir. Bu verilerden yola çıkarak dipiron’un anksiyolitik etki gösterebileceği düşünüldü; varsa bu etkisinde kannabinoid ve TRPV1 reseptörlerinin katkısının araştırılması planlandı.Gereç ve Yöntem: Balb-c farelerde dipiron (150, 300, 600 mg/kg, i.p.) verildikten sonra üç odalı sosyallik ve sosyal yenilik testi, açık alan testi ve yükseltilmiş artı labirent testleri uygulanması, etki görülürse kannabinoid CB1 antagonisti AM251 (1 mg/kg i.p.), CB2 antagonisti SR 144528 (1 mg/kg i.p.) ve TRPV1 antagonisti kapsazepin (3 mg/kg i.p.) ile birlikte verilmesi düşünüldü. Bulgular: Dipiron herhangi bir dozunda davranış testlerinin (üç odalı sosyallik ve sosyal yenilik testi, açık alan testi ve yükseltilmiş artı labirent testi) hiçbirisinde etki göstermedi. Bu nedenle, dipiron ile birlikte kannabinoid CB1, CB2 ve TRPV1 reseptör antagonistlerinin birlikte uygulanacağı aşamaya geçilmedi.Sonuç: Parasetamol’den farklı olarak, dipiron farelerde anksiyolitik-benzeri etkilere yol açmamaktadır. Deneysel modeller ve ölçüm yöntemlerindeki farklılıklar bu bulgularımızın nedeni olabilir.

Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms. Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism. Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme. In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.