title: Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats.
abstract: Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals' nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3-L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals' nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression.
authors: Laboratório de Anestesiologia Experimental, Faculdade de Medicina da Universidade de São Paulo.
authors: José Oswaldo
authors: JO
authors: de Oliveira Junior
authors: Departamento de Anatomia do Instituto de Ciências Biomédicas da Universidade de São Paulo.
authors: Milena Fernandes
authors: MF
authors: de Freitas
authors: Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors: Carolina
authors: C
authors: Bullara de Andrade
authors: Departamento de Anatomia do Instituto de Ciências Biomédicas da Universidade de São Paulo.
authors: Marucia
authors: M
authors: Chacur
authors: Laboratório de Anestesiologia Experimental, Faculdade de Medicina da Universidade de São Paulo.
authors: Hazem Adel
authors: HA
authors: Ashmawi
keywords: naloxone; opioid receptors; postoperative pain; rats; tramadol