Hyaluronic Acid an Option for Neuropathic Pain Management?

Nonsurgical option available to treat Peyronie's disease
Nonsurgical option available to treat Peyronie’s disease
Off-label use of commercially available cosmetic cross-linked hyaluronic acid provided relief in patients with neuropathic pain.

NATIONAL HARBOR, Md. — Patients with neuropathic pain that were treated with cross-linked hyaluronic acid (HA) injections experienced reductions in Visual Analog Scale of Pain (VAS) scores, findings from a small study examining off-label use of the medication indicated. 

Hyaluronic acid injections are commonly used as fillers in cosmetic surgical procedures and are commercially available as Restylane and Perlane (Medicis) and Juvéderm Ultra and Juvéderm Ultra Plus (Allergan). They are approved by the US Food and Drug Administration (FDA) for the temporary correction of moderate-to-severe facial wrinkles and folds.

John A. Campa III, MD, an attending neurologist at the Neuropathic Pain Center for Clinical Research and Treatment in Albuquerque, New Mexico, performed a 34-month retrospective chart review to examine the safety and efficacy of cross-linked HA among 15 patients with persistent, neuropathic pain who were treated off-label with HA injections.1 He presented his findings during a poster session at theAmerican Academy of Pain Management 2015 meeting.

Average pain duration among study participants was 66 months. A total of 22 separate neuropathic pain syndromes were identified. Pain locations included the face (n=1), spine (n=6), cervical (n=1), thoracic (n=3), lumbosacral (n=2), shoulder (n=1), elbow (n=2), wrist (n=2), thigh (n=2) and feet (n=9). 

All patients underwent differential local anesthetic neural blockade to determine the most reactive neural point to identify the relevant peripheral nerve innervating the painful area. Patients were injected with cross-linked HA at a fixed HA concentration of 24 mg/mL and a variable cross-linking value of 9% to 11%. The average dose was 0.5 cc and was administered via  a 27 gauge needle or a variable length blunt tip 27 gauge microcannula after a 20 gauge injection port was prepared. 

All patients reported pain relief with an average post-procedure VAS pain score of 1.5 out of 10 (range: 0-3.5). Average time to achieve pain relief was 24 hours (range: 0-48 hours) and average pain relief duration was 7.7 months (range: 2.5-18). No patients reported adverse events.

“Patients benefited on measures of pain reduction, promptness of pain reduction, and the duration of pain reduction,” said Dr. Campa. 

The mechanisms underlying these findings are likely multifactorial and require additional study, according to Dr. Campa. He proposed several potential mechanisms of action including cross-linked HA as a physical, protective shielding and compartment;2 anionic depolarization;3 and intercellular adhesion molecule-1 inflammatory modulation.4

“Targeted, neural matrix antinocicipetion injection of cross-linked hyaluronic acid should be considered early in the treatment of patients with neuropathic pain,” said Dr. Campa. 


  1. Campa JA. “Cross-Linked Hyaluronic Acid: A Paradigm Shift in the Treatment of Neuropathic Pain.” Presented at: AAPM 2015. Sept. 17-20; National Harbor, Maryland. 
  2. Vorvolakos K, Isayeva IS, Do Luu HM, Patwardhan D et al. “Ionically cross-linked hyaluronic acid: wetting, lubrication, and viscoelasticity of a modified adhesion barrier gel.” Med Devices (Auckl). 2011;4:1-10. 
  3. Chen WY, Abatangelo G. “Functions of hyaluronan in wound repair.” Wound Repair Regen. 1999; 7(2):79-89. 
  4. Tajerian M, Clark JD. “The role of extracellular matrix in chronic pain following injury.” Pain. 2015; 156(3):366-370.