Background & Aims

Primary somatosensory neurons in the dorsal root ganglion (DRG) play an essential role in the induction and maintenance of pain, but how injury of nerves affects adjacent, uninjured DRG neuron activity at a population level remains unknown. Coupled activation of adjacent DRG neurons has previously been shown to be partially mediated by injury-induced upregulation of gap junctions in DRG glial cells and blocking those gap junctions reduced injury-induced pain.

Methods

Sciatic Nerve Ligation Injury (SNL): The lumbar 5 sciatic nerve is surgically exposed and loosely ligated with 1 sutures and the incision in closed with 4-0 suture. Sham surgery mice have no sutures on the sciatic nerve.
Pain tests von Frey (vF), Hargreaves (Hg), and Cold Plantar (CP): Mice’s right hind paw are subjected to pressure from a von Frey filament and the threshold to rapidly withdraw the paw 50% of the time is calculated using the up and down method.Radiant heat is shined on the right hind paw through glass or dry ice is pressed against the glass directly below the right hind paw. Behavior testings were performed on days 1 and 7 after SNL.
In vivo Ca2+ imaging: Mice are kept anesthetized on day 8 after SNL. The Lumbar 5 (L5) DRG is surgically exposed and placed on a custom stage with the right hind paw is left exposed. Laser Scanning confocal Microscopy (LSM) is performed. Mechanical and chemical stimuli were applied to the right hind paw or DRG during imaging.

Results

According to our findings, the lumbar-5 SNL produced coupled activation in both L5 and adjacent, uninjured L4 DRGs. In vivo Ca+2 imaging showed that SNL increased the total numbers and proportion of neurons showing coupled activation. Blocking gap junctions with carbenoxolone (CBX) attenuated neuronal coupling and hypersensitization of the DRG neurons.

Conclusions

Coupled activation of adjacent DRG neurons has previously been shown to be partially mediated by injury-induced upregulation of gap junctions in DRG glial cells and blocking those gap junctions reduced injury-induced pain. Further studies will be conducted to delve into the role of coupled activation in neuronal activation and pain sensitization.

References

1.Liem, L., et al., The Dorsal Root Ganglion as a Therapeutic Target for Chronic Pain. Reg Anesth Pain Med, 2016. 41(4): p. 511-9.
2.von Hehn, C.A., R. Baron, and C.J. Woolf, Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron, 2012. 73(4): p. 638-52.
3.Hanani, M., Intercellular communication in sensory ganglia by purinergic receptors and gap junctions: implications for chronic pain. Brain Res, 2012. 1487: p. 183-91.
4.Kim, Y.S., et al. Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain. Neuron, 2016. 91:p.1085-1096.

Presenting Author

Ruben Gomez

Poster Authors

Ruben Gomez

BSc

University of Texas Health Science Center at San Antonio

Lead Author

E-mail

Topics

  • Pain Imaging