TY - JOUR

T1 - Stress sensitivity and cutaneous sensory thresholds before and after neuropathic injury in various inbred and outbred rat strains

AU - Hestehave, Sara

AU - Abelson, Klas SP

AU - Brønnum Pedersen, Tina

AU - Munro, Gordon

PY - 2019/12/16

Y1 - 2019/12/16

N2 - Chronic pain is associated with altered affective state, stress, anxiety and depression. Conversely, stress, anxiety and depression can all modulate pain perception. The relative link between these behavioural constructs in different inbred and outbred rat strains, known to be variously hypo/hyperresponsive to stress has not been determined. Hindpaw sensory thresholds to repeated mechanical (von Frey filament and electronic Randall Selitto) and thermal (Hargreaves, cold plate and hot plate) stimulation were routinely assessed over three weeks in non-injured male rats of the following strains; WKY, LEW, F344, Hsd:SD and Crl:SD. Thereafter, threshold responses to Spared Nerve Injury (SNI) were assessed using von Frey, pin prick and Hargreaves testing in the same strains over a three month period. Finally, anxiolytic efficacy of the benzodiazepine drug diazepam was assessed using the Elevated Plus Maze (EPM), as a surrogate index of functional plasticity of circuits involved in affective processing. Repeated nociceptive testing was associated with distinct strain-dependent changes in sensory thresholds in naïve rats; stress-hyporesponsive LEW rats presented with a mechanical/thermal hyperalgesia phenotype, whereas stress-hyperresponsive WKY rats presented with an unexpected heat/cold hypoalgesia phenotype. After SNI, LEW rats showed minimal signs of neuropathic sensitivity. Diazepam was anxiolytic in all tested strains with the exception of LEW rats reflecting distinct inherent affective processing only in this strain. The contribution of stress reactivity to nociceptive sensory profiles appears to vary in the absence or presence of neuropathic injury. Intriguingly, the functional responsiveness of affective state prior to injury may be a predisposing factor to developing chronic pain.

AB - Chronic pain is associated with altered affective state, stress, anxiety and depression. Conversely, stress, anxiety and depression can all modulate pain perception. The relative link between these behavioural constructs in different inbred and outbred rat strains, known to be variously hypo/hyperresponsive to stress has not been determined. Hindpaw sensory thresholds to repeated mechanical (von Frey filament and electronic Randall Selitto) and thermal (Hargreaves, cold plate and hot plate) stimulation were routinely assessed over three weeks in non-injured male rats of the following strains; WKY, LEW, F344, Hsd:SD and Crl:SD. Thereafter, threshold responses to Spared Nerve Injury (SNI) were assessed using von Frey, pin prick and Hargreaves testing in the same strains over a three month period. Finally, anxiolytic efficacy of the benzodiazepine drug diazepam was assessed using the Elevated Plus Maze (EPM), as a surrogate index of functional plasticity of circuits involved in affective processing. Repeated nociceptive testing was associated with distinct strain-dependent changes in sensory thresholds in naïve rats; stress-hyporesponsive LEW rats presented with a mechanical/thermal hyperalgesia phenotype, whereas stress-hyperresponsive WKY rats presented with an unexpected heat/cold hypoalgesia phenotype. After SNI, LEW rats showed minimal signs of neuropathic sensitivity. Diazepam was anxiolytic in all tested strains with the exception of LEW rats reflecting distinct inherent affective processing only in this strain. The contribution of stress reactivity to nociceptive sensory profiles appears to vary in the absence or presence of neuropathic injury. Intriguingly, the functional responsiveness of affective state prior to injury may be a predisposing factor to developing chronic pain.

KW - Anxiety

KW - Diazepam

KW - Neuropathic pain

KW - Pain

KW - Strain-differences

UR - http://www.scopus.com/inward/record.url?scp=85071096264&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2019.112149

DO - 10.1016/j.bbr.2019.112149

M3 - Journal article

C2 - 31419521

AN - SCOPUS:85071096264

VL - 375

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

M1 - 112149

ER -