Pain
-
Randomized Controlled Trial
Inflammation-induced pain sensitization in men and women: Does sex matter in experimental endotoxemia?
A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. ⋯ Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes.
-
Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. ⋯ In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes.
-
Patients with chronic pain often report their cognition to be impaired by pain, and this observation has been supported by numerous studies measuring the effects of pain on cognitive task performance. Furthermore, cognitive intrusion by pain has been identified as one of 3 components of pain anxiety, alongside general distress and fear of pain. Although cognitive intrusion is a critical characteristic of pain, no specific measure designed to capture its effects exists. ⋯ The scale had high internal reliability and a clear 1-component structure. It differentiated between chronic pain and control groups, and it was a significant predictor of pain-related disability over and above pain intensity. Repairing attentional interruption from pain may become a novel target for pain management interventions, both pharmacologic and nonpharmacologic.
-
It is well documented that borderline personality disorder (BPD) is characterized by reduced pain sensitivity, which might be related to nonsuicidal self-injury and dissociative experiences in patients with BPD. However, it remains an open question whether this insensitivity relies at least partly on altered sensory integration or on an altered evaluation of pain or a combination of both. In this study, we used the thermal grill illusion (TGI), describing a painful sensation induced by the application of alternating cold and warm nonnoxious stimuli, in patients with either current or remitted BPD as well as matched healthy controls. ⋯ Thermal grill illusion magnitude was negatively correlated with dissociation and traumatization only in the current BPD patients. These results indicate that higher-order pain perception is altered in current BPD, which seems to normalize after remission. We discuss these findings against the background of neurophysiological evidence for the TGI in general and reduced pain sensitivity in BPD and suggest a relationship to alterations in N-methyl-D-aspartate neurotransmission.
-
Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. ⋯ Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation.