Postoperative neuropathic pain is a common problem, even if the patient is in the best condition. Like other types of nerve injury pain, neuropathic pain after surgery is difficult to treat and usually relies on adjuvant analgesics, such as antidepressants and anticonvulsants, and nerve blockers. I developed a treatment using commercially available cross-linked hyaluronic acid (Restylane and Juvéderm), which provides long-lasting, significant relief without side effects.
Cross-linked hyaluronic acid was used for the first time to treat neuropathic pain at the 2015 Annual Meeting of the American Academy of Pain Medicine in National Harbor, Maryland. 1 In a 34-month retrospective chart review, 15 neuropathic pain patients (7 women, 8 men) and 22 pain syndromes were studied. The average age of the patients was 51 years and the average duration of pain was 66 months. The average visual analog scale (VAS) pain score before treatment was 7.5 points (out of 10). After treatment, VAS dropped to 10 points (out of 1.5), and the average duration of remission was 7.7 months.
Since I introduced my original work, I have treated 75 patients with similar pain syndromes (ie, post-herpetic neuralgia, carpal tunnel and tarsal tunnel syndrome, Bell’s paralytic tinnitus, headache, etc.). Due to the possible mechanism of action at work, I designated this treatment as cross-linked neural matrix analgesia (XL-NMA). 2 I provide a case report of a patient with persistent neck and hand pain after cervical spine surgery.
Hyaluronic acid (HA) is a proteoglycan, a linear anionic polysaccharide 3 composed of repeating units of glucuronic acid and N-acetylglucosamine. It is naturally present in the extracellular matrix (ECM) (56%) of the skin, 4 connective tissue, epithelial tissue and nerve tissue. 4,5 In healthy tissues, its molecular weight is 5 to 10 million daltons (Da)4.
Cross-linked HA is a commercial cosmetic approved by the FDA. It is sold under the brands Juvéderm6 (manufactured by Allergan, HA content 22-26 mg/mL, molecular weight 2.5 million daltons)6 and Restylane7 (manufactured by Galderma), and the HA content is 20 mg/ Milliliters, the molecular weight is 1 million Daltons. 8 Although the natural non-crosslinked form of HA is a liquid and is metabolized within a day, the molecular crosslinks of HA combine its individual polymer chains and form a viscoelastic hydrogel, so its service life (6 to 12 Months) and moisture absorption capacity can absorb 1,000 times its weight of water. 5
A 60-year-old man came to our office in April 2016. After receiving C3-C4 and C4-C5 posterior cervical decompression, posterior fusion, local autotransplantation and posterior segmental internal fixation, the neck continued And bilateral hand pain. Quality screws at C3, C4, and C5. His neck injury occurred in April 2015, when he fell backwards at work when he hit his neck with his head and felt his neck thump.
After the operation, his pain and numbness became more and more serious, and there was continuous severe burning pain in the back of his hands and neck (Figure 1). During the flexion of his neck, severe electric shocks radiated from his neck and spine to his upper and lower limbs. When lying on the right side, the numbness of the hands is most severe.
After performing computed tomography (CT) myelography and radiography (CR) tests, cervical segmental lesions were found at C5-C6 and C6-C7, which will support the continuous pain in the hands and the occasional mechanical nature of neck flexion Pain (ie, secondary neuropathic and spinal pain states and acute C6-C7 radiculopathy).
Specific lesions affect bilateral nerve roots and related spinal cord segments in front, including:
The spine surgeon accepted the consultation, but felt that there was nothing to offer for another operation.
In late April 2016, the patient’s right hand received Restylane (0.15 mL) treatment. The injection is performed by placing a port with a 20 gauge needle, and then inserting a 27 gauge microcannula (DermaSculpt) with a blunt tip. For comparison, the left hand was treated with a mixture of 2% pure lidocaine (2 mL) and 0.25% pure bupivacaine (4 mL). The dose per site is 1.0 to 1.5 mL. (For step-by-step instructions on this process, see the sidebar.) 9
With some modifications, the injection method is similar to the conventional nerve block at the wrist level of the median nerve (MN), ulnar nerve (UN), and superficial radial nerve (SRN) at the anatomical level. Snuff box-the triangular area of the hand formed between the thumb and middle finger. Twenty-four hours after the operation, the patient found continuous numbness in the palms of the fourth and fifth fingers of the right hand but no pain. Most of the numbness in the first, second and third fingers disappeared, but there was still pain in the fingertips. Pain score, 4 to 5). The burning sensation on the back of the hand has completely subsided. Overall, he felt an improvement of 75%.
At 4 months, the patient noticed that the pain in his right hand was still improved by 75% to 85%, and the side numbness of fingers 1 and 2 was tolerable. There are no adverse reactions or effects. Note: Any relief from the local anesthesia in the left hand was resolved 1 week after the operation, and his pain returned to the baseline level of that hand. Interestingly, the patient noticed that although the burning pain and numbness on the top of the left hand after injection of the local anesthetic had subsided, it was replaced by a very unpleasant and annoying numbness.
As mentioned earlier, the patient reported that after receiving XL-NMA, the neuropathic pain in the right hand was significantly improved. The patient visited again in late August 2016, when he reported that the improvement began to diminish in late July 2016. He proposed an enhanced XL-NMA intervention for the right hand, as well as XL-NMA treatment for the left hand and the cervical-brachial area-bilateral, proximal shoulder, C4 area and C5-C6 level.
The patient visited again in mid-October 2016. He reported that after the intervention in August 2016, his burning pain in all painful areas was sustained and completely relieved. His main complaints are dull/severe pain on the surface of the palm and back of the hand (different pain sensations-some are sharp and some are dull, depending on the nerve fibers involved) and tightness around the wrist. The tension was due to damage to the nerve roots of his cervical spine, which involved the fibers that form all 3 main nerves (SRN, MN, and UN) in the hand.
The patient noticed a 50% increase in cervical spine rotational range of motion (ROM), and a 50% reduction in cervical and arm pain in the C5-C6 and C4 proximal shoulder area. He proposed XL-NMA augmentation of bilateral MN and SRN-the UN and neck-brachial area remained improved without treatment.
Table 1 summarizes the proposed multifactorial mechanism of action. They are ranked according to their closeness to the time-varying anti-nociception—from the most direct effect in the first 10 minutes after injection to the lasting and prolonged relief observed in some cases a year or more.
CL-HA acts as a physical protective barrier, forming a compartment, attenuating the activation of spontaneous activities in C fiber and Remak bundle afferents, as well as any abnormal nociceptive ephapse. 10 Due to the polyanionic nature of CL-HA, its large molecules (500 MDA to 100 GDa) may completely depolarize the action potential due to the magnitude of its negative charge and prevent any signal transmission. LMW/HMW mismatch correction leads to TNFα-stimulated gene 6 protein regulation area inflammation. This stabilizes and restores the immune neural crosstalk disorder at the level of the extracellular neural matrix, and basically prevents the factors that are believed to cause chronic pain. 11-14
Essentially, after extracellular neural matrix (ECNM) injury or injury, there will be an initial acute phase of obvious clinical inflammation, accompanied by tissue swelling and activation of Aδ and C fiber nociceptors. However, once this condition becomes chronic, tissue inflammation and immune nerve crosstalk will become persistent but subclinical. Chronicization will occur through re-entry and a positive feedback loop, thereby maintaining and maintaining the pro-inflammatory, pre-pain state, and preventing entry into the healing and recovery phase (Table 2). Because of the LMW/HMW-HA mismatch, it can be self-sustaining, which may be the result of CD44/CD168 (RHAMM) gene aberrations.
At this time, the injection of CL-HA can correct the LMW/HMW-HA mismatch and cause circulatory interruption, allowing interleukin (IL)-1β and TNFα to induce TSG-6 to regulate inflammation, by regulating and down-regulating LMW-HA and CD44. This then allows normal progression to the ECNM anti-inflammatory and analgesic phase, because CD44 and RHAMM (CD168) are now able to interact with HMW-HA correctly. To understand this mechanism, see Table 2, which illustrates the cytokine cascade and neuroimmunology associated with ECNM injury.
In summary, CL-HA can be regarded as a super-giant Dalton form of HA. Therefore, it has repeatedly enhanced and maintained the body’s HMW-HA recovery and healing molecular biology standard functions, including:
When discussing this case report with my colleagues, I was often asked, “But how does the effect change in the peripheral treatment far away from the neck lesion?” In this case, the known lesions of each CR and CT myelography Recognition at the level of spinal cord segments C5-C6 and C6-C7 (C6 and C7 nerve roots, respectively). These lesions damage the nerve root and the anterior part of the spinal cord, so they are a close part of the known source of the radial nerve root and spinal cord (ie, C5, C6, C7, C8, T1). And, of course, they will support the constant burning pain on the back of the hands. However, in order to further understand this, the concept of incoming incoming must be considered. 16
Afferent neuralgia is simply, “…Despite reduced or insensitivity to external noxious stimuli (hypoalgesia or analgesia) to the body part, severe spontaneous pain in the distal body part of the injury.” 16 It may Caused by any damage to the nervous system, both central and peripheral, including the brain, spinal cord, and peripheral nerves. The afferent nerve is thought to be due to the loss of information from the periphery to the brain. More specifically, there is an interruption in the afferent sensory information that reaches the cortex through the spinothalamic tract. The domain of this bundle includes the transmission of pain or nociceptive input concentrated to the thalamus. Although the precise mechanism is still poorly understood, the model is very suitable for the situation at hand (ie, these nerve roots and spinal cord segments are not completely afferent to the radial nerve).
Therefore, applying it to the burning pain on the back of the patient’s hand, according to the mechanism 3 in Table 1, injury must occur to initiate the pro-inflammatory, pre-noxious state of the cytokine cascade (Table 2). This will come from physical damage to the affected nerve roots and spinal cord segments. However, since ECNM is a continuous and diffuse neuroimmune entity that surrounds all neural structures (ie, it is a whole), the affected sensory neurons of the affected C6 and C7 nerve roots and spinal cord segments are continuous and Limb contact and neuroimmune contact on the back of both hands.
Therefore, the damage in the distance is essentially the result of the strange effect of the proximal ECNM in the distance. 15 This will cause CD44, CD168 (RHAMM) to detect HATΔ, and release IL-1β, IL-6 and TNFα inflammatory cytokines, which activate and maintain the activation of distal C fibers and Aδ nociceptors when appropriate (table 2, #3). With the damage of ECNM around the distal SRN, XL-NMA can now be successfully used for in situ intervention to achieve CL-HA LMW/HMW-HA mismatch correction and ICAM-1 (CD54) inflammation regulation (Table 2, # 3-#5 cycle).
Nevertheless, it is indeed gratifying to reliably obtain lasting relief from severe and stubborn symptoms through safe and relatively minimally invasive treatments. The technique is usually easy to perform, and the most challenging aspect may be identifying the sensory nerves, neural networks, and the substrate to be injected around the target. However, with technology standardization based on common clinical manifestations, this is not difficult.
I described the application and technique of cross-linked hyaluronic acid targeted SRN nerve matrix analgesic injection in the successful treatment of dorsal neuropathic pain in the hands of a 60-year-old injured worker undergoing posterior cervical decompression. This technology brings lasting relief and has proven to be a safe and effective method for the patient. We recommend that you consider using it routinely as early as possible to manage pain in similar patients.
Post time: Aug-12-2021