Discovering chronic pain treatments: better animal models might help us get there
Norman E. Taylor, Luiz Ferrari
Norman E. Taylor, Luiz Ferrari
Published March 1, 2023
Citation Information: J Clin Invest. 2023;133(5):e167814. https://doi.org/10.1172/JCI167814.
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Commentary

Discovering chronic pain treatments: better animal models might help us get there

Abstract

Only three classes of pain medications have made it into clinical use in the past 60 years despite intensive efforts and the need for nonaddictive pain treatments. One reason for the failure involves the use of animal models that lack mechanistic similarity to human pain conditions, with endpoint measurements that may not reflect the human pain experience. In this issue of the JCI, Ding, Fischer, and co-authors developed the foramen lacerum impingement of trigeminal nerve root (FLIT) model of human trigeminal neuralgia that has improved face, construct, and predictive validities over those of current models. They used the FLIT model to investigate the role that abnormal, hypersynchronous cortical activity contributed to a neuropathic pain state. Unrestrained, synchronous glutamatergic activity in the primary somatosensory cortex upper lip and jaw (S1ULp–S1J) region of the somatosensory cortex drove pain phenotypes. The model establishes a powerful tool to continue investigating the interaction between the peripheral and central nervous systems that leads to chronic pain.

Authors

Norman E. Taylor, Luiz Ferrari

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Figure 1

Coordination of glutamatergic activity in the somatosensory cortex drives neuropathic pain phenotypes.

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Coordination of glutamatergic activity in the somatosensory cortex drive...
(A) Somatosensory afferent information from the face is transmitted from the trigeminal ganglion via the trigeminothalamic tract to S1. In the absence of nociceptor activation in the territory covered by the trigeminal ganglion, GABA, which is tonically released by interneurons, binds to GABA receptors on glutamatergic neurons in the S1ULp–S1J region, which produce asynchronous glutamatergic neuron activity. (B) Impingement of the trigeminal nerve root at the foramen lacerum by surgically introducing a gelatin sponge in mice replicates symptoms of human TN. A lack of GABA secretion via GABAergic interneurons releases the functional inhibition of glutamatergic neurons, increasing glutamate within the extracellular space and contributing to an excitatory response. Synchronous glutamatergic neuron activity in the S1ULp–S1J region produces symptoms of TN.