Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation-induced sensitisation of central nociceptive pathways.

ABSTRACT: The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. The only mechanical QST z -score profiles that demonstrated a consistent gain of function across repeated test sessions were mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), which were associated with moderate and good reliability, respectively. There was no relationship between HFS intensity and MPT and MPS z -score profiles. There was no change in low intensity, but a consistent facilitation of high-intensity pin prick stimuli in the mechanical stimulus response function across repeated test sessions. There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.

Assessment of Somatosensory Function and Self-harm in Adolescents.

Importance: Self-harm is a risk factor for suicide in adolescents, with the prevalence highest in young people in group and residential care programs. Although no established risk factors for self-harm exist, adolescents who self-harm may have decreased pain sensitivity, but this has not been systematically investigated. Objective: To assess somatosensory function using quantitative sensory testing (QST) in children and adolescents living in care grouped by the number of episodes of self-harm in the past year and compare their somatosensory profiles with community control participants to investigate associations with the incidence or frequency of self-harm. Design, Setting, and Participants: Recruitment for this cross-sectional study began January 2019 and ended March 2020. Exclusion criteria included intellectual disability (intelligence quotient <70), autism spectrum disorder, or recent serious injury. Children and adolescents aged 12 to 17 years with no underlying health conditions were recruited from local authority residential care settings in Glasgow, UK, and schools and youth groups in London and Glasgow, UK. The volunteer sample of 64 participants included adolescents ages 13 to 17 years (34 [53%] females; 50 [78%] living in residential care; mean [SD] age, 16.34 [1.01] years) with varying incidents of self-harm in the past year (no episodes, 31 [48%]; 1-4 episodes, 12 [19%]; and ≥5 episodes, 2 [33%]). Exposures: Participants were tested using a standardized QST protocol to establish baseline somatosensory function. Main Outcomes and Measures: Associations between somatosensory sensitivity, incidence and frequency of self-harm, residential status, age, gender, and prescription medication were calculated. Secondary outcomes assessed whether self-harm was associated with specific types of tests (ie, painful or nonpainful). Results: A total of 64 participants ages 13 to 17 years completed testing (mean [SD] age, 16.3 [1.0] years; 34 [53%.] females and 30 [47%] males; 50 [78%] living in group homes). Adolescents with 5 or more self-harm incidences showed significant pain hyposensitivity compared with community control participants after adjusting for age, gender, and prescription drug use (SH group with 5 or more episodes vs control: -1.03 [95% CI, -1.47 to -0.60]; P < .001). Hyposensitivity also extended to nonpainful stimuli, similarly adjusted (SH group with 5 or more episodes vs control: -1.73; 95% CI, -2.62 to -0.84; P < .001). Pressure pain threshold accounted for most of the observed variance (31.1% [95% CI, 10.5% to 44.7%]; P < .001). Conclusions and Relevance: The findings of this study suggest that sensory hyposensitivity is a phenotype of Adolescents who self-harm and that pressure pain threshold has clinical potential as a quick, inexpensive, and easily interpreted test to identify adolescents at increased risk of repeated self-harm.

Unilateral pyramidotomy of the corticospinal tract in rats for assessment of neuroplasticity-inducing therapies.

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has great importance for distal muscle control in humans and, to a lesser extent, in rodents. A unilateral cut of one pyramid results in loss of CST innervation of the spinal cord mainly on the contralateral side of the spinal cord leading to transient motor disability in the forelimbs and sustained loss of dexterity. Ipsilateral projections of the corticospinal tract are minor. We have refined our surgical method to increase the chances of lesion completeness. We describe postsurgical care. Deficits on the Montoya staircase pellet reaching test and the horizontal ladder test shown here are detected up to 8 weeks postinjury. Deficits on the cylinder rearing test are only detected transiently. Therefore, the cylinder test may only be suitable for detection of short term recovery. We show how, electrophysiologically and anatomically, one may assess lesions and plastic changes. We also describe how to analyse fibers from the uninjured CST sprouting across the midline into the deprived areas. It is challenging to obtain >90% complete lesions consistently due to the proximity to the basilar artery in the medulla oblongata and survival rates can be low. Alternative surgical approaches and behavioural testing are described in this protocol. The pyramidotomy model is a good tool for assessing neuroplasticity-inducing treatments, which increase sprouting of intact fibers after injury.