High-frequency modulation of rat spinal field potentials: effects of slowly conducting muscle vs. skin afferents

Abstract

Zhang J, Hoheisel U, Klein T, Magerl W, Mense S, Treede RD. High-frequency modulation of rat spinal field potentials: effects of slowly conducting muscle vs. skin afferents. J Neurophysiol 115: 692-700, 2016. First published November 11, 2015 doi:10.1152/jn.00415.2015 in rat spinal dorsal horn neurons was induced by electrical high-frequency stimulation (HFS) of afferent C fibers. LTP is generally assumed to be a key mechanism of spinal sensitization. To determine the contribution of skin and muscle afferents to LTP induction, the sural nerve (SU, pure skin nerve) or the gastrocnemiussoleus nerve (GS, pure muscle nerve) were stimulated individually. As a measure of spinal LTP, C-fiber-induced synaptic field potentials (SFPs) evoked by the GS and by the SU were recorded in the dorsal horn. HFS induced a sustained increase of SFPs of the same nerve for at least 3 h, indicating the elicitation of homosynaptic nociceptive spinal LTP. LTP after muscle nerve stimulation (HFS to GS) was more pronounced (increase to 248%, P Ͻ 0.05) compared with LTP after skin nerve stimulation (HFS applied to SU; increase to 151% of baseline, P Ͻ 0.05). HFS applied to GS also increased the SFPs of the unconditioned SU (heterosynaptic LTP) significantly, whereas HFS applied to SU had no significant impact on the SFP evoked by the GS. Collectively, the data indicate that HFS of a muscle or skin nerve evoked nociceptive spinal LTP with large effect sizes for homosynaptic LTP (Cohen's d of 0.8 -1.9) and small to medium effect sizes for heterosynaptic LTP (Cohen's d of 0.4 -0.65). The finding that homosynaptic and heterosynaptic LTP after HFS of the muscle nerve were more pronounced than those after HFS of a skin nerve suggests that muscle pain may be associated with more extensive LTP than cutaneous pain.

Pathophysiology of musculoskeletal pain: a narrative review

“…Recent evidence suggests that greater homosynaptic and heterosynaptic LTP develop in a context of muscle pain than in cutaneous pain. 35 Consistent with these observations, afferent sensory fibers express increased numbers of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors after repetitive stimulation. 36 Several mechanisms have been proposed to explain central neuronal hyperexcitability.…”

Rat dorsal horn neurons primed by stress develop a long-lasting manifest sensitization after a short-lasting nociceptive low back input

“…10 Additional C-fiber input was likely activated by the mechanical stimuli used, 18 but this was not verified by electrical search stimuli because we were concerned that such stimuli may induce long-term potentiation. 63 Of the 60 neurons recorded, 45 (75%) responded to at least 1 of the mechanical test stimuli used (control 1 NGF: n 5 21, stress 1 NGF: n 5 24); 15 neurons (25%) responded to the electrical search stimulus but could not be activated by the test stimuli applied to the low back and hind limb (Table 1, without RFs). Of the 45 responding neurons, 36% (16 of 45) received input from deep tissues, 84% (38 of 45) input from the skin, and 20% (9 of 45) had convergent input.…”

Tenderness of the Skin after Chemical Stimulation of Underlying Temporal and Thoracolumbar Fasciae Reveals Somatosensory Crosstalk between Superficial and Deep Tissues

“…Notably, very shortly after Clifford Woolf—based on electrophysiological animal experiments—had first proposed that central sensitization contributed to hyperalgesia [ 56 ], further experiments by his group suggested that nociceptive input from deep tissue rather than from cutaneous inputs may be more efficient to induce this synaptic facilitation in the spinal dorsal horn [ 33 , 57 ]. Human psychophysical data suggest that modulation of pain sensitivity between muscle and fascia is bidirectional and asymmetric, since strong muscle pain (delayed onset muscle soreness) facilitated pain sensitivity of the fascia [ 58 ], while painful fascia stimulation did not modulate muscle pain sensitivity [ 11 ].…”

“…Human psychophysical data suggest that modulation of pain sensitivity between muscle and fascia is bidirectional and asymmetric, since strong muscle pain (delayed onset muscle soreness) facilitated pain sensitivity of the fascia [ 58 ], while painful fascia stimulation did not modulate muscle pain sensitivity [ 11 ]. The stimulation of nociceptive afferents of a muscle nerve facilitated nociceptive dorsal horn field potentials elicited by skin nerve stimulation, but not vice versa [ 57 ]. Moreover, muscle pain could blunt heterotopic deep pain sensitivity [ 59 ] and even the weak muscle pain induced by electrical high frequency stimulation heterotopically reduced the pain sensitivity of the fascia [ 11 ].…”