Articles: hyperalgesia.
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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.
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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.
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Menopausal and postmenopausal women, characterized by a significant reduction in ovarian hormones, have a high prevalence of chronic pain with great pain intensity. However, the underlying mechanism of hyperalgesia induced by ovarian hormone withdrawal remains poorly understood. ⋯ Moreover, activation of the DRNGABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRNGABA neurons and their modulation by estrogen in regulating hyperalgesia induced by ovarian hormone withdrawal, providing therapeutic basis for the treatment of chronic pain in physiological or surgical menopausal women.
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Diabetic neuropathy is a prevalent and debilitating complication of diabetes, necessitating effective pain management strategies. While pharmacological treatments, including opioids, are commonly employed, they pose significant challenges due to the risk of developing opioid-induced hyperalgesia (OIH). This case report aims to illustrate the efficacy of a comprehensive, multidisciplinary approach in managing painful diabetic neuropathy complicated by OIH. ⋯ Effective management of OIH involves gradual opioid tapering and a multimodal therapeutic approach. However, the optimal treatment strategies and the frequency of OIH occurrence remain areas of uncertainty, relying heavily on clinical expertise and individualized patient care. Further research is needed to refine these treatment strategies and improve patient outcomes.
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Review Meta Analysis
Systematic review and co-ordinate based meta-analysis to summarize the utilization of functional brain imaging in conjunction with human models of peripheral and central sensitization.
Functional magnetic resonance imaging, in conjunction with models of peripheral and/or central sensitization, has been used to assess analgesic efficacy in healthy humans. This review aims to summarize the use of these techniques to characterize brain mechanisms of hyperalgesia/allodynia and to evaluate the efficacy of analgesics. ⋯ Experimental pain models that provide a surrogate for features of pathological pain conditions in healthy humans and functional imaging techniques are both highly valuable research tools. This review shows that when used together, they provide a wealth of information about brain activity during pain states and analgesia. These tools are promising candidates to help bridge the gap between animal and human studies, to improve translatability and provide opportunities for identification of new targets for back-translation to animal studies.