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Injection of Juvederm Treats Neuropathic Pain

Persistent neuropathic pain presents a special challenge for clinicians. Current treatments—opioids, antineuropathic pain adjuvants, and nerve blocks—often offer only modest pain control and are limited by side effects. A new study has found that commercially available cross-linked hyaluronic acid (Restylane, Juvéderm) may result in prolonged pain relief, with no real side effects, according to John A. Campa III, MD, Attending Neurologist, Clinical Neurosciences, Albuquerque, New Mexico.1

Dr. Campa has treated 15 patients with 22 different pain syndromes with cross-linked hyaluronic acid (CL-HA), injecting it at the level of the neural matrix. After the treatment, most of the patients “have no pain, with an average duration [of analgesia] of 8 months from a single injection,” he told Practical Pain Management.

During the study, Dr. Campa enrolled 15 patients with persistent neuropathic pain lasting, on average, 5.5 years. The location of treatment varied, from the face to the foot. Of the 22 pain syndromes treated in the study, 9 were in the feet; other conditions included post-herpetic neuralgia, paroxysmal low back pain and bilateral buttock pain without any spinal lesions, intercostal pain, as well as pain due to tarsal tunnel syndrome, postsurgical neuritis, herniated discs in the neck, biceps tendon injury, and supraspinatus tendinopathy in the left shoulder.

To identify the location for treatment, Dr. Campa first injected a local anesthetic (0.5-2.5 mL plain lidocaine) to determine the point overlying the peripheral nerve running through the painful area. If the patient had a positive response (pain relief greater than 50%), he scheduled a treatment session 1 week later, allowing time for the anesthetic nerve block to wear off.

Treatment consisted of, where necessary, placing a port with a 21-gauge needle, and then inserting a 27-gauge microcannula with a blunt tip. “I do this so I can approach the nerve from three-quarters of an inch away, nudge the nerve to verify appropriate paresthesia in the area of pain, then inject the CL-HA.” The needle is then withdrawn and the area is massaged. “You have to massage the area because CL-HA is a relatively viscous material—it’s a hydrogel—and the idea is to spread the gel over that nerve territory along its long axis.” (see Figures 1-3) Cross-linked HA is FDA-approved for cosmetic use at higher doses, but the doses used for pain management are miniscule—about 0.07 to 0.15 mL, noted Dr. Campa. “Since, for the most part, these are superficially accessible nerves, ultrasound guidance is not needed; you just need to know your neuroanatomy.”

Of the 15 patients treated, all achieved pain relief within 48 hours, with the average time to relief being 24 hours. Visual Analogue Pain scores decreased from an average of 7.5 before treatment to 1.5 after treatment.

To illustrate the effectiveness of the treatment, Dr. Campa described a case of a woman with diabetic neuropathy. “The woman had foot pain over the tops of her feet, which is usually the territory of the superficial peroneal nerve, but pain also extended all the way up to her knees. I decided to place the injection in the ankle area first [to] easily access the superficial peroneal nerve. Fifteen minutes after the injection, all of her pain was gone, both the pain in the foot and up to the knees.”

How Does It Work?

Dr. Campa has proposed possible mechanisms to explain the effectiveness of CL-HA. He said that it appears to work at the level of the extracellular neural matrix. The hydrogel may act as a physical protective shielding that forms a compartment that blunts the activation of spontaneous activity in the C fibers and the Remak bundle afferent nerves, as well as aberrant nociceptive ephapse. Another possible theory is that because CL-HA is a massive molecule (300 to 400 million Daltons), it “may completely depolarize the action potential due to the size of its negative charge, and, therefore, there can’t be any transmission of the signal,” he said.

Dr. Campa predicted, however, that the mechanism behind CL-HA’s efficacy is going to be found to be multifactorial. “Cross-linked HA augments the known HA intercellular adhesion molecule-1 [ICAM-1], resulting in modulation of the regional, inflammatory response,” he said. This stabilizes and restores “the post-injury, immunoneural cross-talk dysregulation at the level of the extracellular neural matrix, essentially blocking what is thought to be causing the chronification of pain.” This, he added, would explain how “someone who’s had diabetic neuropathic pain for 15 years can be treated with a single local injection and have that [pain relief] last 8 months to 2 years. I call this a paradigm shift in the treatment of neuropathic pain.”

Underscoring the revolutionary nature of these ideas, Dr. Campa said, “I believe we have to rethink all of our current models of understanding chronic widespread pain. I accept that patients with chronic pain undergo microglial changes and neuroplasticity, but are these CNS events really sustaining the problem, as we’ve thought for years? Or is the problem really in the extracellular neural matrix where the injury or disease occurred? There’s some abnormal molecular biology going on that sustains the nociceptive signal flowing up the spinal cord to the brain, which then causes the changes in the microglia—so those CNS changes occur after the fact.” Dr. Campa concluded that targeted, neural sensory “antinociception injection” of CL-HA is a safe and effective method of treating neuropathic pain.

Reference

  1. Campa JA. Cross-linked hyaluronic acid—a paradigm shift in the treatment of neuropathic pain. Presented at: American Academy of Pain Medicine, National Harbor, MD, March 19-22, 2015. Poster LB001.

 

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