Pain Pathways and Pain Physiology

Pain is a multidimensional sensory experience that is mediated by complex peripheral and central neuroanatomical pathways and mechanisms. Typically, noxious stimuli activate specific peripheral nerve terminals onto Aδ‎ and C nerve fibers that convey pain and generate signals that are relayed and processed in the spinal cord and then conveyed via the spinothalamic tracts to the contralateral thalamus and from there to the brain. Acute pain is self-limited and resolves with the healing process, but conditions of extensive injury or inflammation sensitize the pain pathways and generate aberrant, augmented responses. Peripheral and central sensitization of neurons (as a result of spatially and temporally excessive inflammation or intense afferent signal traffic) may result in hyperexcitability and chronicity of pain, with spontaneous pain and abnormal evoked responses to stimuli (allodynia, hyperalgesia). Finally, neuropathic pain follows injury or disease to nerves as a result of hyperexcitability augmented by various sensitizing mechanisms.

Respiratory modulation of startle eye blink: a new approach to assess afferent signals from the respiratory system

Current approaches to assess interoception of respiratory functions cannot differentiate between the physiological basis of interoception, i.e. visceral-afferent signal processing, and the psychological process of attention focusing. Furthermore, they typically involve invasive procedures, e.g. induction of respiratory occlusions or the inhalation of CO 2 -enriched air. The aim of this study was to test the capacity of startle methodology to reflect respiratory-related afferent signal processing, independent of invasive procedures. Forty-two healthy participants were tested in a spontaneous breathing and in a 0.25 Hz paced breathing condition. Acoustic startle noises of 105 dB(A) intensity (50 ms white noise) were presented with identical trial frequency at peak and on-going inspiration and expiration, based on a new pattern detection method, involving the online processing of the respiratory belt signal. The results show the highest startle magnitudes during on-going expiration compared with any other measurement points during the respiratory cycle, independent of whether breathing was spontaneous or paced. Afferent signals from slow adapting phasic pulmonary stretch receptors may be responsible for this effect. This study is the first to demonstrate startle modulation by respiration. These results offer the potential to apply startle methodology in the non-invasive testing of interoception-related aspects in respiratory psychophysiology. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

Hypohydration and muscular fatigue of the thumb alter median nerve somatosensory evoked potentials

The mechanisms by which dehydration impairs endurance performance remain unresolved but may involve alterations in afferent neural processing. The purpose of this study was to determine the effect of hypohydration on somatosensory evoked potentials (SEPs) at rest and during recovery from fatiguing exercise. Fourteen volunteers (12 men, 2 women) performed repetitive isometric thumb contractions (50% maximal voluntary contractions (MVC) and 100% MVC in a 5:1 ratio, each contraction separated by 5 s of rest) until exhaustion when euhydrated (EU) and when hypohydrated by 4% body mass (HY). SEPs were obtained from the median nerve. The results indicated that HY did not produce statistical differences in time to exhaustion (EU = 754 (SD 255); HY = 714 (SD 318) s; p = 0.66) or rate of muscle fatigue. However, HY was associated with greater subjective feelings of fatigue and loss of vigor after exhaustive exercise (p < 0.01). HY affected N20 latency with an interaction effect of hydration by fatigue state (EU-Rest: 18.5 (SD 1.6) ms; EU-Fatigue: 19.0 (SD 1.6) ms; HY-Rest: 18.3 (SD 1.3) ms; HY-Fatigue: 18.4 (SD 1.5) ms; p = 0.034), but N20 and N20-P22 amplitude responses were similar between HY and EU trials. We concluded that moderate water deficits appear to alter afferent signal processing within the cerebral cortex.

Stimulus-Specific and Stimulus-Nonspecific Firing Synchrony and Its Modulation by Sensory Adaptation in the Whisker-to-Barrel Pathway

The stimulus-evoked response of a cortical neuron depends on both details of the afferent signal and the momentary state of the larger network in which it is embedded. Consequently, identical sensory stimuli evoke highly variable responses. Using simultaneous recordings of thalamic barreloid and/or cortical barrel neurons in the rat whisker-to-barrel pathway, we determined the extent to which the responses of pairs of cells covary on a trial-by-trial basis. In the thalamus and cortical layer IV, a substantial component of trial-to-trial variability is independent of the specific parameters of the stimulus, probed here using deflection angle. These stimulus-nonspecific effects resulted in greater-than-chance similarities in trial-averaged angular tuning among simultaneously recorded pairs of barrel neurons. Such effects were not observed among simultaneously recorded thalamic and cortical barrel neurons, suggesting strong intracortical mechanisms of synchronization. Sensory adaptation produced by prior whisker deflections reduced response magnitudes and enhanced the joint angular tuning of simultaneously recorded neurons. Adaptation also decorrelated stimulus-evoked responses, rendering trial-by-trial responses of neuron pairs less similar to each other. Adaptation-induced decorrelation coupled with sharpened joint tuning could enhance the saliency of cells within thalamus or cortex that continue to fire synchronously during ongoing tactile stimulation associated with active touch.