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Cross-Linked Hyaluronic Acid Injection for Neuropathic Pain

Case presentation and superficial radial nerve injection technique
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Postsurgical neuropathic pain is a frequent problem, even if the patient was in the best of hands. As with other types of nerve injury pain, postsurgical neuropathic pain is difficult to treat, usually relying on adjuvant pain medications, such as antidepressants and anticonvulsants, and nerve blocks. I have developed a treatment method that uses commercially available cross-linked hyaluronic acid (Restylane and Juvéderm) that provides prolonged, significant relief without side effects.

The first use of cross-linked hyaluronic acid to treat neuropathic pain was presented at the 2015 Annual Meeting of the American Academy of Pain Medicine in National Harbor, Maryland.1 In the 34-month retrospective chart review, 15 neuropathic pain patients (7 women, 8 men) with 22 pain syndromes were studied. The average age of the patients was 51 years, with a mean pain duration of 66 months. The pretreatment average visual analog scale (VAS) pain score was 7.5 out of 10. After treatment, the VAS was reduced to 1.5 out of 10, and the average duration of relief was 7.7 months.

Use of cross-linked hyaluronic acid to treat neuropathic pain.

Since I presented my original work, I have treated an additional 75 patients with similar pain syndromes (ie, postherpetic neuralgia, carpal tunnel and tarsal tunnel syndrome, Bell’s Palsy tinnitus and head pain, etc). Due to the likely mechanisms of action at work, I have designated this method of treatment as Cross-Linked Neural Matrix Antinociception (XL-NMA).I present a case report of a patient with persistent neck and hand pain after undergoing cervical spine surgery.

Molecular Structure

Hyaluronic acid (HA), a proteoglycan, is a linear anionic polysaccharide3 composed of glucuronic acid and N-acetylglucosamine repeating units. It naturally occurs throughout the extracellular matrix (ECM) of the skin (56%),4 connective, epithelial, and neural tissues.4,5 Its molecular weight is 5 to 10 million Dalton (Da)4 in healthy tissues.

Cross-linked HA is an FDA-approved, commercially available cosmetic agent, which is marketed under the brand names Juvéderm6 (manufactured by Allergan, HA content 22-26 mg/mL, molecular weight 2.5 million Da)6 and Restylane7 (manufactured by Galderma, HA content 20 mg/mL, molecular weight 1 million Da).8 While the native, non-cross-linked form of HA is a liquid and metabolized in a day, the molecular cross-linking of the HA  binds its individual polymeric chains and forms a viscoelastic hydrogel, accounting for its longevity (6 to 12 months) and its hygroscopic ability to absorb 1,000 times its weight in water.5

Case Report

A 60-year-old male came to our office in April 2016 with persistent neck and bilateral hand pain after undergoing posterior cervical spine decompression at C3-C4, C4-C5, with posterior fusion, local autograft, and posterior segmental instrumentation, with lateral mass screws at C3, C4, C5. His neck injury occurred in April 2015 after a backward fall at work, when he struck his head and felt a pop in his neck.

Postoperatively, he developed increasing pain and numbness, with severe constant burning pain to the dorsa of both hands and neck (Figure 1). During anteroflexion of his neck, severe electric-like shocks radiated down his neck and spine to both upper and lower extremities. The numbness in his hands was most severe when lying on his right side.

After computed tomography (CT) myelography and radiographic (CR) testing were performed, cervical spinal segmental lesions were identified at C5-C6 and C6-C7 that would support the ongoing pain to both hands and incident, mechanical pain upon neck flexion (ie, a secondary neuropathic and myelopathic pain state and acute C6-C7 radiculopathy).

Specific lesions affected both the nerve roots bilaterally and related spinal cord segments anteriorly, which included:

  • C5-C6: Diffuse disc osteophyte complex (bone spurs) effaced the contrast (material) anterior to the spinal cord, with effacement of the contrast surrounding each exiting C6 nerve root and expected encroachment of the exiting C6 nerves bilaterally.
  • C6-C7: Diffuse disc osteophyte complex effaced contrast anterior to the spinal cord, with flattening of the anterior spinal cord. Also noted was severe bilateral osseous foraminal narrowing with encroachment of both exiting C7 nerve roots.

The spine surgeon was consulted but felt there was nothing further to offer by performing another surgery.


In late April 2016, the patient’s right hand was treated with Restylane (0.15 mL). The injectate was administered by placing a port with a 20-gauge needle, and then inserting a 27-gauge microcannula (DermaSculpt) with a blunt tip. To compare, the left hand was treated with a mixture of 2% plain lidocaine (2 mL) and 0.25% plain bupivacaine (4 mL). The dose per site was 1.0 to 1.5 mL. (See the sidebar for a step-by-step description of this procedure.)9

With some modifications, the method for injection is similar to that used for routine nerve blocks at the level of the wrist of the median nerve (MN), ulnar nerve (UN), and superficial radial nerve (SRN) at the level of the anatomical snuffbox—the triangular area of the hand formed between the thumb and second finger. Twenty-four hours after the procedure, the patient noted that digits 4 and 5 on his right hand had persistent palmar numbness but no pain, while in digits 1, 2, and 3, most of the numbness was gone but his fingertips still hurt (pain score, 4 to 5). The burning numbness in the dorsal hand had completely resolved. Overall, he felt 75% improved.

At 4 months, the patient noted his right-hand pain remained 75% to 85% improved, with a tolerable level of numbness in the lateral aspects of digits 1 and 2. There were no untoward reactions or effects. Note: Any relief from the local anesthetic administered to the left hand had resolved 1 week after the procedure, with his pain returning to baseline in that hand. Interestingly, the patient noted that although the burning numbness pain on the top of his left hand had resolved after local anesthetic injection, it was replaced by a very unpleasant, annoying sensation of numbness.

Follow-up Treatments

As noted, the patient reported dramatic improvement in neuropathic pain in the right hand after undergoing XL-NMA. The patient was seen again in late August 2016, when he reported that the improvement began to wane in late July 2016. He presented for augmentation XL-NMA intervention on the right hand, and XL-NMA treatment of the left hand as well as the cervicobrachial region—bilateral, proximal shoulder, C4 region, and C5-C6 level.

Last updated on: June 15, 2017
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