Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats

Abstract

Concerns over interactions between analgesics and experimental outcomes are a major reason for withholding opioids from rats undergoing surgical procedures. Only a fraction of morphine injected intravenously reaches receptors responsible for analgesia in the central nervous system. Intrathecal administration of morphine may represent a way to provide rats with analgesia while minimizing the amount of morphine injected. This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain (caudal laparotomy).In an initial blinded, randomised study, pain-free rats received morphine subcutaneously (MSC, 3mg.kg-1, N = 6), intrathecally (MIT, 0.2mg.kg-1, N = 6); NaCl subcutaneously (NSC, N = 6) or intrathecally (NIT, N = 6). Previously validated pain behaviours, activity and Rat Grimace Scale (RGS) scores were recorded at baseline, 1, 2, 4 and 8h post-injection. Morphine-treated rats had similar behaviours to NaCl rats, but their RGS scores were significantly different over time and between treatments. In a second blinded study, rats (N = 28) were randomly allocated to one of the following four treatments (N = 7): MSC, 3mg.kg-1, surgery; MIT, 0.2mg.kg-1, surgery; NIT, surgery; NSC, sham surgery. Composite Pain Behaviours (CPB) and RGS were recorded as previously. CPB in MIT and MSC groups were not significantly different to NSC group. MSC and MIT rats displayed significantly lower RGS scores than NIT rats at 1 and 8h postoperatively. RGS scores for MIT and MSC rats were not significantly different at 1, 2, and 8h postoperatively. Intraclass correlation value amongst operators involved in RGS scoring (N = 9) was 0.913 for total RGS score. Intrathecal morphine was mostly indistinguishable from its subcutaneous counterpart, providing pain relief lasting up to 8 hours in a rat model of surgical pain. Further studies are warranted to clarify the relevance of the rat grimace scale for assessing pain in rats that have received opioid analgesics.

Performance of behavioral assays: the Rat Grimace Scale, burrowing activity and a composite behavior score to identify visceral pain in an acute and chronic colitis model

“…The behaviors evaluated (writhe, twitch, back arch, belly pressing, and fall/stagger) were previously validated in rats subjected to a laparotomy and were suggested as a potential tool to assess visceral pain. 26,29 The incidence of some of these same behaviors has also been observed to increase in ureteral calculi and intestinal mucositis models. 10,33 However, a slightly different combination of behaviors was observed in each model.…”

“…The CBS consisted of recording the frequency of 5 behaviours (writhing, vertical back arching, stagger/fall, twitch, and belly pressing) as described by Roughan and Flecknell 26 and Thomas et al 29 Writhing behavior was defined as the contraction of the abdominal muscles. Back arching was defined as a vertical stretch upward that resembled a cat stretching.…”

Evans Blue Reduces Neuropathic Pain Behavior by Inhibiting Spinal ATP Release

“…Intrathecal injection—the intrathecal injection was performed using aseptic techniques according to a previous report [46]. In brief, the injection site was between the last lumbar vertebra and the first sacral vertebrae (L6–S1).…”

Neuronal and glial factors contributing to sex differences in opioid modulation of pain

“…Opioid receptors are densely populated within all three regions, and administration of opioids can elicit analgesia at each of these target sites [26][27][28][29][30][31][32]. Although the PAG, RVM, and spinal cord dorsal horn are all critical for opioid modulation of pain, this review focuses on the PAG as numerous lines of evidence indicate that the PAG is a primary site for opiate action.…”