Pain
-
Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. ⋯ Using a structural model of NaV1.7, we were also able to provide further insight into the structural mechanisms underlying fast inactivation and the role of the C-terminal domain in this process. Our observations suggest that rare NaV1.7 variants contribute to the development NeuP in patients with DPN. Their identification should aid understanding of sensory phenotype, patient stratification, and help target treatments effectively.
-
Primary burning mouth syndrome (BMS) is defined as an "intraoral burning or dysaesthetic sensation, recurring daily… more than 3 months, without clinically evident causative lesions" (IHS 2013). In addition to pain, taste alterations are frequent (dysgeusia, xerostomia). Although lacking clinical signs of neuropathy, more accurate diagnostic methods have shown neuropathic involvement at various levels of the neuraxis in BMS: peripheral small fiber damage (thermal quantitative sensory testing, electrogustatometry, epithelial nerve fiber density), trigeminal system lesions in the periphery or the brainstem (brainstem reflex recordings, trigeminal neurography, evoked potentials), or signs of decreased inhibition within the central nervous system (deficient brainstem reflex habituation, positive signs in quantitative sensory testing, neurotransmitter-positron emission tomography findings indicative of deficient striatal dopamine function). ⋯ According to these findings, the clinical entity of BMS can be divided into 2 main subtypes compatible with either peripheral or central neuropathic pain, which may overlap in individual patients. The central type does not respond to local treatments and associates often with psychiatric comorbidity (depression or anxiety), whereas the peripheral type responds to peripheral lidocaine blocks and topical clonazepam. Burning mouth syndrome is most prevalent in postmenopausal women, having led to a hypothesis that BMS is triggered as a consequence of nervous system damage caused by neurotoxic factors affecting especially vulnerable small fibers and basal ganglia in a setting of decrease in neuroprotective gonadal hormones and increase in stress hormone levels, typical for menopause.
-
Research shows that chronic pain is related to cortical alterations that can be reflected in reduced tactile acuity, but whether acute pain perception influences tactile acuity has not been tested. Considering the biological role of nociception, it was hypothesized that nociceptive pain will lead to a rapid improvement in tactile acuity and that this effect is correlated with pain intensity and pain distribution. In this randomised double-blind controlled experiment (trial no. ⋯ Other tests, point-to-point test and two-point estimation task, changed with a similar trend but did not reach significance. We concluded that acute, nociceptive pain does not improve but deteriorates tactile acuity linearly. The biological role of the observed phenomenon is unknown, and therefore, future studies should address this question.
-
Nerve growth factor (NGF) injected into the human skin causes local hyperalgesia to mechanical and electrical stimuli lasting for weeks. Pig data suggested axonal sensitization of C-nociceptors as a contributing mechanism. Here, we recorded single C-nociceptors in 11 human subjects 3 weeks after intracutaneous injection of 1 μg NGF into the foot dorsum. ⋯ The sensitization included sensory and axonal components affecting both activation thresholds and supra-threshold responses. Our data suggest that a combination of sensory sensitization and axonal hyperexcitability is underlying the localized hyperalgesia by facilitating action potential generation and conduction. Axonal changes were also found in the asymptomatic skin surrounding the NGF-treatment sites, thereby possibly reflecting "nociceptive priming."