Intrathecal Oxytocin Improves Spontaneous Behavior and Reduces Mechanical Hypersensitivity in a Rat Model of Postoperative Pain

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.

Stress during the COVID-19 Pandemic Moderates Pain Perception and Momentary Oxytocin Levels

“…In line with previous studies [ 26 ], we did not find any role of sex in the association of oxytocin and pain. Although in animal models, oxytocin has been shown to directly decrease pain signaling to the spinal cord [ 39 , 40 ], it has also been suggested to elicit stress-induced hyperalgesia [ 13 ]. Furthermore, our observation of stress as a moderator of endogenous oxytocin effects is consistent with a previous study showing that higher levels of plasma oxytocin were associated with fewer depressive symptoms and more sensitive maternal behavior among women who reported high levels of psychosocial stress [ 41 ].…”

In Vivo Dissection of Two Intracellular Pathways Involved in the Spinal Oxytocin-Induced Antinociception in the Rat

“…Finally, it is interesting to point out that our results suggest that this neuropeptide could act as a pre-emptive analgesic. These results agree with a previous report showing that intrathecal injection of this neuropeptide prevents the development of postsurgical nociception . Nevertheless, at this point, we do not know if the same mechanisms elicited to prevent the long-lasting nociception (i.e., allodynia) will be operative when the oxytocin is given as a curative treatment (when the allodynia is fully established).…”

“…These results agree with a previous report showing that intrathecal injection of this neuropeptide prevents the development of postsurgical nociception. 20 Nevertheless, at this point, we do not know if the same mechanisms elicited to prevent the long-lasting nociception (i.e., allodynia) will be operative when the oxytocin is given as a curative treatment (when the allodynia is fully established). In any case, more experiments designed to tackle this question are necessary.…”

Oxytocin Is a Positive Allosteric Modulator of κ-Opioid Receptors but Not δ-Opioid Receptors in the G Protein Signaling Pathway

“…One weakness of this study is that we did not analyze the interaction of oxytocinergic and opioidergic neuronal systems using animal pain models. Many studies have demonstrated that OT improves pain in several animal models [30,32,34,58]. In addition, some reports have shown that activation of the OT receptor upregulates preproenkephalin gene expression, which is the precursor for enkephalin, the endogenous ligand for MOR [59,60].…”