# scFv Antibody Therapy for Chronic Trigeminal Neuropathic Pain

> **NIH NIH R21** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $189,625

## Abstract

Abstract
Chronic orofacial neuropathic pain that persists after motor vehicle accidents and other facial injuries can be
excruciating, unrelenting, and a difficult clinical challenge. Sensitized nerves in the face overactivate not only the
trigeminal ganglia neurons but also the second order trigeminal spinal V dorsal horn neurons and glia. Continued
activation of pain transmission circuitry results in central sensitization and can exert powerful dysfunctional
influences at brain sites associated with anxiety and PTSD. Chronic pain can induce permanent brain circuitry
alterations that further diminish physical and mental function. Current treatment with analgesics combined with
antidepressants and/or anticonvulsants are generally unsatisfactory in providing pain relief. While opiates are
heavily overprescribed to the point of national crisis, they are of little therapeutic value for treatment of orofacial
pain. Effective non-addictive, non-opioid therapeutics for chronic orofacial pain remain a critical need.
Experimental models in which pain signaling pathways are chronically activated by mild traumatic injury to the
trigeminal nerve offer a compelling avenue for discovery and development of new non-addictive, non-opioid
therapies. In our trigeminal neuropathic orofacial pain mouse model the trigeminal nerve is compressed to mimic
post-traumatic orofacial neuropathic pain in patients. Our recent gene profiling revealed significant 4.0- and 2.7-
fold increases in cholecystokinin B (CCK-B) receptor gene expression in the trigeminal ganglia at 3 and 21 days,
respectively. The proposed collaborative, multidisciplinary studies will develop novel, brain-penetrant single-
chain Fragment variable (scFv) antibody therapies to block CCK-B receptor activation. Aim 1 proposes to
generate a repertoire of scFv antibodies using cell-free ribosome display technology to develop, characterize,
and authenticate a panel of antibodies to block CCK-B receptor activation. The Aim 2 studies propose testing
optimal CCK-B receptor scFv antibodies as therapy to alleviate reflexive and cognitive dependent pain- and
anxiety-related behaviors in our orofacial pain model. Preliminary data demonstrate the effectiveness of a single
dose of CCK-B receptor scFv antibody administered 3 weeks after model induction during the transition from
acute to chronic pain. The proposed studies will further test efficacy of scFv antibody therapy at 8 weeks when
hypersensitivity is chronic. Addition of a fluorescent tag on the scFv antibodies will allow additional experimental
read-outs including biodistribution with in vivo imaging and postmortem neuropathology to characterize the
neuronal and glial cell types involved and their localization.
Hypothesis: scFv antibody block of CCK-B receptors is effective therapy for chronic orofacial pain.
Aim 1. Generate a panel of CCK-B receptor-specific single-chain Fragment variable (scFv) antibodies
using cell-free ribosome display technology to develop...

## Key facts

- **NIH application ID:** 9912752
- **Project number:** 5R21DE028096-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Adinarayana Kunamneni
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,625
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912752

## Citation

> US National Institutes of Health, RePORTER application 9912752, scFv Antibody Therapy for Chronic Trigeminal Neuropathic Pain (5R21DE028096-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9912752. Licensed CC0.

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