Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.
Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30weeks) after transection and immediate end-to-end reconstruction of the sciatic nerve in rats. These findings were compared to the density of epidermal (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw. Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks PO, a time point in which both subgroups of epidermal nerve fibers reached control values. Thermal hypersensitivity was observed with simultaneous increase in the density of epidermal peptidergic nerve fibers of the contralateral hind paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve fibers returned to control values 30weeks PO. We conclude that changes in skin innervation and sensitivity are present on the uninjured corresponding side in a transient pain model. Therefore, the contralateral side cannot serve as control. Moreover, the current study confirms the involvement of the peripheral nervous system in the development of mirror-image pain.
Dept. of Neuroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands; Dept. of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: s.kambiz@erasmusmc.nl.
S
S
Kambiz
Dept. of Neuroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands; Dept. of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
E M
EM
Brakkee
Dept. of Neuroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands; Dept. of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
L S
LS
Duraku
Dept. of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
S E R
SE
Hovius
Dept. of Neuroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
T J H
TJ
Ruigrok
Dept. of Plastic Surgery, Radboud UMC, Nijmegen, The Netherlands.
E T
ET
Walbeehm
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D004576:Electromyography; D004817:Epidermis / Q000473:pathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology; D009412:Nerve Fibers / Q000502:physiology*; D020932:Nerve Growth Factor / Q000627:therapeutic use; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010455:Peptides; D051381:Rats; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D012585:Sciatica / Q000503:physiopathology*; D012867:Skin / Q000294:innervation*; D013997:Time Factors
D010455:Peptides; D058477:Receptors, Purinergic P2X3; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide
Epidermal sensory nerve fibers; Mirror-image pain; Non-peptidergic nerve fibers; Peptidergic nerve fibers; Transient neuropathic pain model