Psychophysical Evidence for Long-Term Potentiation of C-Fiber and Aδ-Fiber Pathways in Humans by Analysis of Pain Descriptors

Abstract

. Long-term potentiation of human pain perception (nociceptive LTP) to single electrical test stimuli was induced by high-frequency stimulation (HFS) of cutaneous nociceptive afferents. Numerical pain ratings and a list of sensory pain descriptors disclosed the same magnitude of nociceptive LTP (23% increase for Ͼ60 min, P Ͻ 0.001), whereas affective pain descriptors were not significantly enhanced. Factor analysis of the sensory pain descriptors showed that facilitation was restricted to two factors characterized by hot and burning (ϩ41%) and piercing and stinging (ϩ21%, both P Ͻ 0.01), whereas a factor represented by throbbing and beating was not significantly increased (ϩ9%, P ϭ 0.47). The increased perception of the burning pain quality for Ͼ1 h after HFS is interpreted as a LTP-like facilitation of the conditioned cutaneous C-fiber pathway. Additionally, the increase of the stinging pain quality supplied evidence for facilitation of a sharpness-sensitive A␦-fiber pathway.

Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans

“…Electrical stimulation is less specific in activating specific nerve fibers, e.g., Aδ-or C-fibers (Nilsson and Schouenborg, 1999;Inui et al, 2002;Mørch et al, 2011). In addition, both C-fiber and Aδ-fiber pathways are found to be involved in the hyperalgesia at the conditioned site after high frequency CES (Hansen et al, 2007). Therefore, CES may inevitably activate both A-δ-and C-fiber nociceptors that are concurrently involved in homosynaptic depression and homosynaptic facilitation mechanisms with unknown net effects (Pfau et al, 2011).…”

“…It has been shown that repetitive activation of primary nociceptive C-fibers leads to a synaptic strengthening of nociceptive transmission which may also induce facilitation of non-nociceptive Aβ-fiber and nociceptive Aδ-fiber pathways resulting in dynamic mechanical allodynia and mechanical hyperalgesia, respectively (Klein et al, 2004;Hansen et al, 2007;van den Broeke et al, 2014 a,b). In the present study pain ratings to pinprick stimuli around the conditioned site were also found to significantly increase from 30 min; most likely as a result of heterosynaptic facilitation of Aδ-pathways.…”

“…It has been shown that high frequency CES (more than 2 bursts at 100 Hz) (Liu and Sandkühler, 1997;Benrath et al, 2005), intermediate frequency CES (10 Hz for 1 sec repeated 12 times at 10 sec interval; 10 Hz for 10 sec) (Terman, 2001;Kim et al, 2015) and even low frequency CES (1~2 Hz for several minutes) (Ikeda et al, 2006;Drdla and Sandkühler, 2008;Kim et al, 2015) of primary afferent C-fibers can induce LTP at the first nociceptive synapses in vivo and in vitro. However, in human subjects the most frequently used paradigm for inducing similar LTP-like pain amplification including homotopic pain-LTP and heterotopic pain-LTP (secondary hyperalgesia) is 1 ms square pulses presented at 100 Hz for 1 sec, repeated 5 times with 10 sec intervals using a special epicutaneous electrode (Klein et al, 2004(Klein et al, , 2006Hansen et al, 2007;Lang et al, 2007;Pfau et al, 2011;van den Broeke et al, 2014 a,b). In contrast, the very low frequency (1 Hz) induced perceptual LTD (long-term depression) rather than LTP (Klein et al, 2004;Rottmann et al, 2010).…”

The Dimensions of Pain Quality: Factor Analysis of the Pain Quality Assessment Scale

“…2,23 That said, however, the only other EFA of pain quality ratings we were able to identify, despite its very low sample size and use of different pain descriptors, found clusters that seem to be similar to those we found in our study. 11 Their EFA of 10 pain qualities resulted in a factor labeled ''superficial pain'' that included 2 descriptors also assessed by the PQAS (sharp and hot) and that loaded on the factor we labeled ''paroxysmal sensations.'' Hansen et al's second factor, labeled ''deep pain,'' included 1 item also assessed by the PQAS (throbbing pain).…”

Neuromechanical representation of fabric-evoked prickliness: a fiber-skin-neuron model

“…Itch is defined as a sensation that evokes a desire to scratch, and prickling or stinging is described as sharp sensations that evoke a reflex desire to withdraw rapidly. Very recently, it has been shown that two independent neural coding mechanisms are involved in so-called itch and prickle sensation in clothing comfort, which might be principally associated with separate coding channels: polymodal C-fiber nociceptors for itch sensation, whereas Ad mechano-sensitive nociceptors (Ad nociceptors in following text, if not pointed, are mechano-sensitive) for prickling sensation as the first pain (Garell et al 1996;Hansen et al 2007). However, understanding of the underlying mechanisms of fabric-evoked itch and prickliness is still far from clear, the main reason being that itch and prickliness is influenced by many factors besides physical features of fiber ends, including both physiological and psychological factors.…”