Before or after mild acute heat exposure – does it matter for the therapy?

Adaptation to elevated temperatures poses a challenge that involves large-scale metabolic changes. It also affects the pharmacokinetics and pharmacodynamics of exogenous substances. Our experiments clearly showed differences in paw pressure thresholds in rats intraperitoneally injected with TDIFELLK—a C-terminal fragment of the calcium-binding, spermatid-specific protein 1—before and after exposure to 38.5 ± 0.5°C, compared to administration at 22 ± 2°C. Similarly, the analgesic effect of the substance, following antagonism of key analgesic receptors—namely opioid, cannabinoid, and serotonergic—was differentially influenced by heat exposure at normal temperature. The administration of the substance before heat exposure exerted a stronger effect than administration after heat exposure.