The journal of pain : official journal of the American Pain Society
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Pain invalidation involves the dismissal or lack of understanding of another's pain, undermining their subjective experience. Frequent exposure to invalidation negatively impacts mental and physical health as well as pain-related behaviors, potentially leading people to conceal their pain from others in the future and/or withdraw from potential sources of support. It is therefore possible that experiencing pain invalidation may also impact pain-reporting behavior in clinical settings. ⋯ Findings provide further evidence for the harmful effects of pain invalidation, particularly for emerging adults, as the dismissal of one's subjective experience may sow self-doubt while reinforcing cultural stigmas against pain, leading to alterations in pain communication that ultimately creates barriers to efficacious clinical treatment and care and increase pain-related suffering. PERSPECTIVE: Pain invalidation imparts harm to those who already suffer from pain, be it mentally, physically, and/or behaviorally. We show that people who have encountered invalidation are more likely to under-rate their pain when seeking care, impeding assessment and treatment, and further highlighting the importance of clinical validation of pain experiences.
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The thermal grill illusion (TGI) describes a peculiar or even painful percept caused by non-noxious, interlaced warm and cold stimuli. It involves the glutamatergic system and is affected in putatively nociplastic syndromes such as fibromyalgia. The glutamatergic system is also involved in wind-up, that is, the increased activation of spinal neurons following repeated noxious stimulation leading to a temporal summation of perceived stimulus intensity. ⋯ These results indicate that although TGI does not involve noxious stimuli it is amenable to temporal summation and wind-up-like processes. Since both phenomena involve the glutamatergic system, the combination of wind-up with the TGI could yield a promising tool for the investigation of chronic pain conditions. PERSPECTIVE: Using thermal stimuli in an experimental protocol to combine 1) the TGI (painful or peculiar percept from simultaneous cold/warm stimulation) and 2) wind-up (increase in stimulus intensity after repeated exposure) holds promise to investigate pain and thermoceptive mechanisms, and chronic pain conditions.
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Lazertinib (JNJ-73841937, YH25448) is a mutant-selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor targeting both the T790M and activating mutation while sparing wild-type epidermal growth factor receptor. Paresthesia is one of the most common adverse events seen with lazertinib treatment, suggesting that lazertinib could affect the sensory nervous system. However, the mechanism of action for this paresthesia remains unclear. ⋯ Collectively, our data suggest a direct effect of lazertinib on nociceptive sensory neurons via TRPA1 selective mechanisms, which could be a putative mechanism of lazertinib-induced sensory abnormalities in clinical patients. PERSPECTIVE: This article presents a TRPA1-dependent, lazertinib-induced activation of mouse sensory neurons in vitro and lazertinib-induced pain-like behaviors in vivo. The same mechanisms may underlie the clinical condition, suggesting that TRPA1 could be a potential therapeutic target to manage lazertinib-induced paresthesia.