Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative and nitrosative stress, an imbalance between reactive oxygen and nitrogen species (ROS/RNS) and antioxidant defenses, plays a crucial role in its pathophysiology. While reactive species are essential for physiological functions, excessive levels can cause cellular component damage, leading to neuronal dysfunction and pain. This review highlights the complex interactions between reactive species, antioxidant systems, cell signaling, and neuropathic pain. We discuss the physiological roles of ROS/RNS and the detrimental effects of oxidative and nitrosative stress. Furthermore, we explore the potential of manganese porphyrins, compounds with antioxidant properties, as promising therapeutic agents to mitigate oxidative stress and alleviate neuropathic pain by targeting key cellular pathways involved in pain. Further research is needed to fully understand their therapeutic potential in managing neuropathic pain in human and non-human animals.

Objective: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. Study design: Randomized, blinded, prospective experimental study. Animals: 98 male Wistar rats. Methods: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL_10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR. Results: Intraperitoneal injection (IP) of maropitant inhibited nociception with ID₅₀ values of 4,1 mg/kg (5,85–19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL_10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). Conclusion and clinical relevance: These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1β. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

We investigated the local and systemic effects of hyperbaric oxygen therapy in BALB/C mice, exposed to two different exposure times, under 2.4 atmosphere (ATM). Fifteen animals were divided into three groups (GI, GII and Control) and underwent a surgical excision of a skin fragment of approximately one square centimeter of the dorsal region. The wounds were treated and monitored for 21 days. In the control group, the wound was cleaned once a day with sterile 0.9% NaCl solution. GI and GII mice were submitted to daily hyperbaric oxygen therapy of 30 or 60minutes sessions, respectively. The wounds were photographed every three days and their surfaces were analyzed by an image analyzer. At 21 days, all animals were euthanatized for histopathological analysis of the skin, lungs and liver in order to identify eventual alterations in wound healing or in the analyzed organs. Animals belonging to GI showed a faster skin wound healing in comparison to the other groups. Animals from GII, however, showed a delayed wound healing process and exhibited lung and microcirculatory alterations. These findings allow us to conclude that the exposure time to the oxygen in hyperbaric environment is crucial and can help or disturb skin wound healing or even be deleterious to other organs.

The aim of this work was to compare three techniques of local blockade, as part of a multimodal protocol in cats submitted to videoassisted ovariectomy (OVH). This study included 38 cats, assigned to four groups (control; incisional block, intraperitoneal block and block of the ovarian arteriovenous complex). Pain was assessed using Analogue Visual Scale, Pain Scale of the UNESP and Composite Multimodal Pains Scale-Feline, prior and after surgery. Anesthetic and analgesic protocols provided adequate post-surgical analgesia in most cats. It is concluded that the intraperitoneal administration of lidocaine may be a useful technique to reduce trans-surgical pain, while the use of incisional infiltration with this medication improves early postoperative pain in videosurgeries.