PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society.
Get the free full text of the selection from the February 2019 issue here.
Papers of the Week is sponsored by the American Pain Society.
Comments
Xinzhong Dong, Johns Hopkins University School of Medicine
This is a very interesting
This is a very interesting study from the labs of Andrew Todd and Mark Hoon that dissects the role of the neuropeptide somatostatin and somatostatin-expressing neurons in itch and pain. Somatostatin is expressed in a small subset of primary sensory neurons in the DRG as well as in many dorsal horn excitatory interneurons. Using a multidisciplinary approach, including optogenetics, chemogenetics, neuronal ablation, and pharmacology, the authors demonstrate that somatostatin+ DRG neurons also express the itch-specific peptide Nppb. Activation of these neurons transmits signals via activation of Npr1 neurons (also expressing GRP) with subsequent activation of GRPR-expressing neurons in the dorsal horn. Strikingly, somatostatin+ DRG neurons suppress certain types of pain. In addition, somatostatin+ dorsal horn neurons also promote itch signal transmission by inhibiting inhibitory interneurons expressing dynorphin, leading to the potentiation of GRPR neurons. These findings suggest a more complex disinhibition mechanism.
This study along with several recent publications support an emerging picture of itch and pain circuits in the spinal cord: instead of a simple linear labeled line, itch and pain signal transmission involves significant cross talk between excitatory and inhibitory interneurons. Therefore, manipulating a group of neurons will affect both itch and pain often in opposing directions. The authors clarified the role of inhibitory B5-I interneurons in suppressing itch, a controversial point reported in previous studies. They showed that it is the dynorphin+ and not NOS+ subset of B5-I neurons that expresses somatostatin receptors and inhibits itch. This study also demonstrates that there are parallel and non-overlapping itch pathways (i.e., Nppb/somatostatin+ versus MrgprA3+ neurons) existing in the periphery. However, both primary itch-sensing neurons converge onto the same secondary neurons (i.e., Npr1/GRP+ neurons) in the dorsal horn (Sun et al., 2017 and the current study). This convergence of peripheral itch pathways is consistent with the current result that manipulating somatostatin/dynorphin neurons in the spinal cord also affects MrgprA3+ neuron-mediated itch such as chloroquine and SLIGRL itch. Finally, the current study and a study by Sun et al. reveal an interesting phenomenon where itch suppresses pain, highlighting a reciprocal push and pull relationship between pain and itch in the spinal cord.