title: Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents.
abstract: Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain.
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina mboada@wakehealth.edu.
authors.forename: M Danilo
authors.initials: MD
authors.lastname: Boada
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gutierrez
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aschenbrenner
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Houle
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Hayashida
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Ririe
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006614:Hindlimb / Q000502:physiology; D008159:Lumbar Vertebrae; D008465:Mechanoreceptors / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials; D009470:Muscle Spindles / Q000294:innervation; D009431:Neural Conduction; D009619:Nociceptors / Q000166:cytology / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology; D014110:Touch
keywords: chronic pain model; in vivo electrophysiology; sensory neurons; spinal nerve ligation