Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury

Abstract

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the nonsteroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (Po0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.

Acanthoscurria gomesiana spider‐derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

“…This may be an appropriate and easily reproducible model for studying neuropathic pain mechanisms and treatments. [ 32,34,45 ] Furthermore, Medeiros and colleagues [ 16 ] showed that the glutamatergic system potentiates chronic NP by NMDAr activation in the PrL cortex. The microinjection of cobalt chloride, a synapse activity blocker, into the PrL cortex decreased the severity of mechanical allodynia, showing late recruitment of the limbic cortex.…”

“…We applied skin stimulation through the mesh, using the tip of a von Frey test rod, targeting the center of the plantar face of the hind paw of each rat until the animal exhibited a withdrawal response. [16,28,[32][33][34][35][36][37]…”

“…For the induction of mononeuropathy in rodents, the Bennett and Xie model [31] adopted by our laboratory team was used, which consists of a singleligature around the nerve. [16,28,[32][33][34][35][36][37] For this procedure, the animals were anesthetized with intramuscular (IM) administration of a solution consisting of 0.1 mL of ketamine at 92 mg/kg and 0.2 mL of xylazine at 9.2 mg/kg. The CCI procedure was performed on the right paw, with the sciatic nerve exposed through dissection of the gluteus maximus muscle and biceps femoris.…”

“…For 5 min, the number of crosses (center, border, and total compartments) and the number of exploratory behaviors (displayed in the center, border, and total compartments) were evaluated. [28,34,36]…”

Estudo do efeito do canabidiol e do envolvimento dos receptores CB1 e 5-HT1A na conexão córtex pré-frontal medial e hipocampo dorsal sobre os aspectos cognitivos e emocionais na dor neuropática crônica em ratos

“…A dor, enquanto objeto de estudo, foi induzida nos roedores a partir de uma cirurgia adaptada, a qual promove uma lesão periférica no nervo ciático. O modelo original, proposto por Bennett & Xie (1988) (BENNETT; XIE, 1988) de quatro ligaduras foi adaptado por Medeiros e colaboradores (2020a, 2021) a uma única ligadura (MEDEIROS et al, 2019a(MEDEIROS et al, , 2019b(MEDEIROS et al, , 2020a(MEDEIROS et al, , 2020b(MEDEIROS et al, , 2020c(MEDEIROS et al, , 2021. A partir desta única ligadura foi demonstrado alterações de limiares nociceptivos bem como alterações comportamentais relacionadas a ansiedade, depressão e cognição, mas sem afetar a capacidade locomotora ou provocar comportamento de autotomia (MEDEIROS et al, 2021).…”