Articles: hyperalgesia.
-
Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. ⋯ In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.
-
Minerva anestesiologica · Feb 2025
Effect of estazolam plus remimazolam on attenuating preoperative anxiety and remifentanil-induced postoperative hyperalgesia in elective gynecological laparoscopic surgery: a randomized clinical trial.
Preoperative anxiety is closely related to opioid-induced hyperalgesia, and high levels of preoperative anxiety have the potential to aggravate opioid-induced hyperalgesia. We aimed to estimate the effect of estazolam, remimazolam, and their combination on preoperative anxiety and opioid-induced hyperalgesia in patients undergoing elective gynecological laparoscopic surgery. ⋯ The preoperative application of estazolam, remimazolam, and their combination can relieve preoperative anxiety and postoperative pain for patients undergoing gynecological laparoscopic surgery. Moreover, the preoperative combination can also significantly reduce postoperative sufentanil consumption.
-
The cerebrospinal fluid-contacting nucleus(CSF-contacting nucleus) is a pair of unique nuclei in the brain parenchyma which has long been demonstrated to play an important role in pain signal processing. However, the mechanisms by which the CSF-contacting nucleus intervenes in pain is unclear. The NRG1-ErbB4 signaling plays an important role in the nervous system and has been shown to be involved in the regulation of pain. ⋯ With immunofluorescence staining and Western blot, the NRG1-ErbB4 signaling in the CSF-contacting nucleus showed upregulated during the acute pain phase. And, activating NRG1-ErbB4 signaling in the CSF-contacting nucleus specifically by intracranial injection of drugs, the naïve mice displayed thermal hyperalgesia while inhibiting this signaling by intracranial injection could reverse the hyperalgesia caused by CSF-contacting nucleus activation, and execute an analgesic effect during the painful phase in mice. Our study suggested that the CSF-contacting nucleus plays a regulatory role in thermal pain in mice via NRG1-ErbB4 signaling.
-
Translational models of the sensitized pain system are needed to progress the understanding of involved mechanisms. In this study, long-term potentiation was used to develop a mechanism-based large-animal pain model. Event-related potentials to electrical stimulation of the ulnar nerve were recorded by intracranial recordings in pigs, 3 weeks before, immediately before and after, and 3 weeks after peripheral high-frequency stimulation (HFS) applied to the ulnar nerve in the right forelimb (7 pigs) or in control animals (5 pigs). ⋯ The relative increase in N1 30 minutes after HFS and the degree of mechanical hyperalgesia 2 weeks post-HFS was correlated ( P < 0.033). These results show for the first time that the pig HFS model resembles the human HFS model closely where the profile of sensitization is comparable. Interestingly, the degree of sensitization was associated with the cortical signs of hyperexcitability at HFS induction.
-
As the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. ⋯ Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain.