Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to maternal separation

in European Journal of Neuroscience (2016)

Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to neonatal maternal deprivation

in European Journal of Neuroscience (2016)

Inter-individual differences in cardiovascular reactivity and the perception of the thermal grill illusion of pain

Speeches/Talks (2015)

Background: Evidence has been given that there exists a functional relationship between the cardiovascular and the pain regulatory system. Alterations in blood pressure and concomitant changes in ... [more ▼]

Background: Evidence has been given that there exists a functional relationship between the cardiovascular and the pain regulatory system. Alterations in blood pressure and concomitant changes in baroreceptor activation contribute to the modulation of pain sensitivity It could be shown that blood pressure, baroreflex sensitivity, and cardiac vagal tone (indexed by heart rate variability, HRV) are inversely associated to pain sensitivity. We aimed assessing the same cardiovascular parameters in a thermal grill paradigm to test the assumption of a relationship between inter-individual differences in autonomic cardiac control and the perception of the thermal grill illusion of pain (TGI). Methods: All participants (N = 52) were stimulated three times during one minute with the temperatures of 15°C and 41°C set at the interlaced cold and warm bars of the water-bath driven thermal grill. Blood pressure and heart rate were recorded concomitantly. Numerical rating scales (NRS; 0–100) were used to quantify subjective paradoxical pain intensity and pain unpleasantness perceptions. Results: A positive association between cardiac vagal tone and paradoxical pain sensitivity could be revealed. Higher resting HRV, as expressed by higher respiratory sinus arrhythmia (RSA), made it overall more likely to perceive the TGI. In contrast, blood pressure and the susceptibility to the TGI were inversely related. Volunteers displaying higher spontaneous blood pressure values in the first thermal grill stimulation phase did not feel the illusive pain as compared to those who presented significantly lower sympathetic arousal and perceived the TGI. Conclusion: The present physiological findings complement previous evidence of an impact of psychological characteristics on the individual disposition to paradoxical pain perceptions. [less ▲]

Prefrontal activation during placebo analgesia is related to cognitive reappraisal

Poster (2015, September)

Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons.

in The European journal of neuroscience (2015)

Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to ... [more ▼]

Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3alpha5alpha-reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase in spinal 3alpha5alpha-reduced steroid production enhancing GABAergic inhibition should reduce nociceptive message integration and the pain response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However, to our knowledge, nothing has been reported regarding direct non-genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma CORT level measurement, to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via a reduction in C-fiber-mediated spinal responses. In the spine, CORT is reduced to the neuroactive metabolite allotetrahydrodeoxycorticosterone, which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of pain. [less ▲]

Pain processing and coping with social stress in rats exposed to adverse early life events

Scientific Conference (2015)

Experimental induction of suffering: why suffering is not the same as unpleasantness

Scientific Conference (2014, October 10)

Introducing the dimension of suffering to mechanically induced phasic and tonic pain

Scientific Conference (2014, October 10)

Vagally mediated heart rate variability is a predictor for the occurrence of the thermal grill-induced pain illusion

Poster (2014, October)

Aim: Unpleasantness and negative affect accompany the sensory experience of pain. Both components of pain are heavily influenced by cognitive and emotional processes. In this framework, alterations in ... [more ▼]

Aim: Unpleasantness and negative affect accompany the sensory experience of pain. Both components of pain are heavily influenced by cognitive and emotional processes. In this framework, alterations in baroreceptor reactivity and concomitant changes in cardiac rhythm and blood pressure related to these processes contribute to the modulation of pain sensitivity. Furthermore, self-regulatory capacity has been shown to play a major role in the regulation of cognitive, affective, and behavioural reactions to adverse contexts. These regulatory mechanisms include adjustment of cardiovascular activity and heavily depend on prefrontal cortical processing. Vagally mediated heart rate variability (HRV) at rest is an indicator of the prefrontally modulated vagal activation and has been used as a psychophysiological marker for self-regulatory capacity. The present study investigated the predictive value of the trait self-regulation in the triggering of the thermal grill-induced pain illusion (TGI). We hypothesized inter-individual differences in paradoxical pain perception to be predicted by self-regulatory capacity in a way that participants displaying lower levels of self-regulation should be more likely to perceive the painful grill illusion than subjects with relatively higher self-regulation ability. Methods: A total of 54 healthy participants were recruited among university students and staff. A custom-built, water-bath driven thermal grill device, with interlaced cold and warm glass tubes, was used for the induction of the TGI. A pre-set temperature combination of 15°C and 41°C was applied to the palm of the dominant hand with stimulus durations of 1 min. Subsequent control conditions consisted in the interlaced combination of a baseline temperature of 32°C with one of the stimulus temperatures mentioned above. The procedure was repeated three times. The volunteers used numerical rating scales ranging from 0-100 to rate sensory and affective pain perceptions in intervals of 15 seconds. Vagally mediated HRV at rest was assessed prior to the thermal stimulation protocols. Results: Time-domain components of HRV used as graded indicators of parasympathetic activity and of the extent of self-regulation significantly predicted the possibility of an occurrence of pain and unpleasantness sensations in response to thermal grill stimulation (p <.05). Participants characterized in this way were more likely to express paradoxical pain than subjects not displaying similar levels of HRV. Conclusion: The present results support previous findings indicating an impact of several psychological traits on the individual disposition to paradoxical pain perceptions. Self-regulation ability, operationalized as vagally mediated heart rate variability, can partially explain the probability of perceived pain in response to non-noxious thermal grill stimulation. [less ▲]

Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II.

in Neuroscience letters (2014), 578

Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs ... [more ▼]

Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3alpha5alpha-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5alpha-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3alpha5alpha-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds. [less ▲]