Testing Assumptions in Human Pain Models: Psychophysical Differences Between First and Second Pain

Abstract

Acute pain arises from activation of myelinated (A delta) and unmyelinated (C) nociceptive afferents, leading to 1st (A-fiber) or 2nd (C-fiber) pain sensations. The current study sought to investigate first and second pain within glabrous and hairy skin sites in human upper-limbs. Fifty healthy adults (25 males/25 females, 18-30 yrs: mean = 20.5 ± 1.4) participated in a psychophysical study investigating electronically rated, thermal first and second pain sensations within the glabrous skin at the palm and hairy skin of the forearm. Repeated measures ANOVA indicated that the threshold for first pain was lower (more sensitive) than for second pain (p = .004), for both glabrous and hairy skin, and thresholds at glabrous skin were higher than for hairy skin (p = .001). Hairy skin presented a steeper slope for testing, whereas there were no differences in slope between first and second pain. The study findings support assumptions associated with mechanistic differences between first and second pain sensations, while offering a novel method for producing first and second pain with the same thermal stimulus. Efforts to understand abnormalities among people with clinical pain and development of new therapeutic agents will benefit from specific psychophysical methods.

Methodological Considerations for the Temporal Summation of Second Pain

“…However, employing the use of temperature optimization for testing may in effect eliminate the ability to detect site differences as theoretically expected. Importantly, the lack of a site difference in the current study is also consistent with our earlier study where site differences were found between the palm and forearm for the temperature for first pain threshold but not second pain threshold[5]. …”

“…; e.g., at the end of each ISI right before the next stimulation) (see Figure 1e) 27 . A similar analysis protocol has been determined effective and used in previous publications[5]. The TESS makes a single recording of thermode temperature and eVAS rating per contact at a preprogramed time point and was set to record at the same time interval as the Pathway.…”

New Insights into Cutaneous Laser Stimulation – Dependency on Skin and Laser Type

“…The greater transparency of the skin would allow the thermal energy of the Nd:YAP laser to be deposited adjacent to the nociceptors located underneath the thick corneous layer of glabrous skin, rather than being absorbed in the most superficial layers of the skin as done by CO2 lasers and contact thermodes. This explanation is also supported by recent evidence that showed that the threshold for first pain elicited by a contact thermode was significant higher in the glabrous skin as compared to the hairy skin (Eckert et al, 2017). In addition, other studies have demonstrated differences in the latencies of laser-evoked brain potentials (LEPs) elicited by CO2 and Nd:YAP laser pulses applied onto the hairy skin (Cruccu et al, 2008), as well as between the latencies of LEPs and contact heat-evoked potentials (CHEPs) (Iannetti et al, 2006).…”

Adaptation to tonic heat in healthy subjects and patients with sensory polyneuropathy

“…Noxious stimuli may cause simultaneous activation of Aδ and C fibres of skin nociceptors, giving rise to two different sensations of pain: the earliest sensation (first pain) is of sharp, stinging quality, while the latest (second pain) is of dull, burning quality (Eckert et al, 2017; Ploner et al, 2002; Price & Dubner, 1977). Probably, these two types of sensation relate also to two different processes occurring when a tonic noxious temperature stimulus is applied: adaptation and sensitization.…”