Abstract
The first few days post-surgery, patients experience intense pain, hypersensitivity and consequently tend to have minor locomotor activity to avoid pain. Certainly, injury to peripheral tissues produces pain and increases sensitivity to painful (hyperalgesia) and non-painful (allodynia) stimuli. In this regard, preemptive pharmacological treatments to avoid or diminish pain after surgery are relevant. Recent data suggest that the neuropeptide oxytocin when given at spinal cord level could be a molecule with potential preemptive analgesic effects, but this hypothesis has not been properly tested. Using a validated postoperative pain model (i.e. plantar incision), we evaluated in male Wistar rats the potential preemptive antinociceptive effects of intrathecal oxytocin administration measuring tactile hypersensitivity (across 8 days) and spontaneous motor activity (across 3 days). Hypersensitivity was evaluated using von Frey filaments, whereas spontaneous activity (total distance, vertical activity episodes, and time spent in the center of the box) was assessed in real time using a semiautomated open-field system. Under these conditions, we found that animals pretreated with spinal oxytocin before plantar incision showed a diminution of hypersensitivity and an improvement of spontaneous behavior (particularly total distance and vertical activity episodes). This report provides a basis for addressing the therapeutic relevance of oxytocin as a potential preemptive analgesic molecule.
Highlights
Every year, ∽240 million people undergo some type of surgery (Weiser et al, 2008; Weiser et al, 2015; Weiser et al, 2016), which causes postoperative pain and distress, and in most cases impairs the patient’s quality life for a brief period (Kehlet and Dahl, 2003)
When comparing the withdrawal threshold of animals pretreated with oxytocin versus untreated animals 1 day after surgery (Figure 1D), we found that the withdrawal threshold of oxytocin-treated rats was higher than that in untreated rats; this result implies a preemptive antinociceptive effect
Using a surrogate model of postoperative pain, this study showed that spinal oxytocin pretreatment induces a diminution in the evoked mechanical hypersensitivity (Figure 1) and an improvement of spontaneous activity (Figures 2, 3)
Summary
Every year, ∽240 million people undergo some type of surgery (Weiser et al, 2008; Weiser et al, 2015; Weiser et al, 2016), which causes postoperative pain and distress (e.g. anxiety), and in most cases impairs the patient’s quality life for a brief period (Kehlet and Dahl, 2003). As discussed by Katz and Seltzer (2009), if acute postoperative pain is reduced, so is the risk of chronic pain This idea points to the relevance of preemptive (or perioperative) analgesia in the management of postsurgical pain. Clinical data showed that the development of chronic pain in women submitted to cesarean is minor in comparison with other non-obstetric interventions (Eisenach et al, 2013) These data, coupled to fact that spinal oxytocin prevents spinal long-term potentiation (LTP) (DeLaTorre et al, 2009), a key process in the development of central sensitization leading to persistent pain (Ruscheweyh et al, 2011), point out the potential role of oxytocin as a preemptive analgesic. The present study was designed to preclinically test the preemptive antinociceptive effect of i.t. oxytocin pretreatment before a surgical procedure in a well-established model of postoperative pain. We found that i.t. pretreatment with oxytocin i) improves spontaneous behavior, ii) improves the recovery time, and iii) diminishes evoked hypersensitivity
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