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15 Articles in Volume 18, Issue #5
Chronic Pelvic Pain: The Need for Earlier Diagnosis and Diverse Treatment
Cross-Linked Hyaluronic Acid for the Management of Neuropathic Pelvic Pain
Fentanyl: Separating Fact from Fiction
Gender Bias and the Ongoing Need to Acknowledge Women’s Pain
Letters to the Editor: 90 MME/day Ceiling; Ehlers-Danlos; Redefining Pain
Post-Menopausal MSK Pain and Quality of Life
PPM Welcomes Dr. Fudin and Dr. Gudin as New Co-Editors
Practitioner as Patient: Understanding Disparities in CRPS
States Take Action to Manage Opioid Addiction
Step-by-Step Injection Technique to Target Endometriosis-Related Neuropathic Pelvic Pain
The Many Gender Gaps in Pain Medicine
The Need for Better Responses to Vulvar Pain
Topical Analgesics for Chronic Pain Conditions
Topical Medications for Common Orofacial Pain Conditions
What’s the safest, effective way to taper a patient off of opioid therapy?

Cross-Linked Hyaluronic Acid for the Management of Neuropathic Pelvic Pain

Case presentation and injection technique targets endometriosis-related pain.
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  1. Endometriosis related-lumbosacral plexopathy, secondary to radicular implants, with secondary neuropathic pain syndrome
  2. High-lumbar lesion with referred pain to hips/pelvis, with secondary radiculopathy
  3. Intermittent mesenteric volvulus and/or internal hernia, with secondary visceral pain syndrome
  4. Metastatic process due to history right breast cancer (7 years prior), lumpectomy.

New Tests Orders and Results

To refine the above differential diagnoses, several tests were ordered. See Table I for diagnostics and results. Based on the new test results, the following determinations were made:

  1. Probable: endometriosis-related lumbosacral radiculoplexopathy, as suggested by EMG plus secondary neuropathic pain syndrome, with referred pain to hips/pelvis
  2. Not found or resolved: intermittent mesenteric volvulus and/or internal hernia
  3. Not found: metastatic process.

Table 1


To localize potential sites for neuromodulation, the patient was scheduled for differential neural blockade with local anesthetic (lidocaine 2%, plain) at: right dorsal cutaneous nerve branches (see Figure 3) of T11, T12, L1, L2, L3, L4, L5, S1, S2, S3, S4. Note: The left-sided pain areas were not treated as the patient felt that the primary pain generators were on the right, and that those sites were referring pain to the left side. See the step-by-step injection technique here.

Figure 3

With the exception of the anterior pelvic region (see patient commentary), the patient reported good relief and began periodic injections at the same sites, with pain control maintained using an injectate of: 4 cc, 2% plain lidocaine; 7.95 cc, 0.25% plain bupivacaine; and 0.25 mg/0.05 cc, morphine sulfate-MSO4 (5 mg/cc), administering 0.5 to 1.5 cc per site. The patient related that these injections, which provided relief for about 7 days, in combination with her opioids improved substantially her ability to perform daily activities, as well as tend to her children and family, including serving as the primary caregiver of her mother who was undergoing treatment for breast cancer. The patient’s reduction in pain was significant (see Figure 4).


Figure 4

XL-NMA – Neural Matrix Aninociception

Approximately 20 months after the patient first presented to the clinic, she underwent an initial trial of XL-neural matrix antinociception at the same sites, using the same technique, except the volumes of the injectate were reduced to one-tenth of the lidocaine/bupivacaine/MSO4 injectate used (this varied from 0.15 cc to 0.25 cc of cross-linked hyaluronic acid, with a concentration varying from 20 mg/ml (Restylane) to 24 mg/ml (Juvederm) per site.11,12 The patient responded well, with no adverse reactions noted, and achieved a duration of relief of 3 to 4 months for the sacral sites, 4 months for the lumbar sites, and 6.5 months for the greater trochanter region. The patient rated overall improvement after the CL-HA injections at 90%. Change in pain scores was remarkable (see Figure 5).

Figure 5

Since that time, the frequency of injection sessions dropped from three to four times per month on the previous injectate of lidocaine/bupivacaine/morphine, to once every five to six months. There have been no adverse reactions and the patient continues on this regimen to date.

Discussion & Recommendations

While the patient’s outcome using cross-linked hyaluronic acid injections was successful, additional research is necessary to elucidate the mechanism of action of this complex substance, as well as to develop additional techniques for its use in neuropathic pain. In this case, the right anterior pelvic pain was essentially unaffected. Methods such as an intercostal T10-12, transforaminal L1, L2, lumbar sympathetic or celiac XL-NMA may be found to remedy this shortcoming.

Mechanism of Action Summary

Purported mechanisms of action are complex and no doubt, multifactorial.13 Nonetheless, it is possible that the antinociceptive effect may occur in a step-wise fashion over time (ie, immediately or in first 10 minutes after injection) and that the CL-HA acts as a physical shield, thereby forming a protective compartment and blunting spontaneous activity of C fiber and Remak bundle afferency, including aberrant nociceptive ephapse.14 In addition, contemporaneous depolarization of the action potential due to its polyanionic nature and size of its negative charge (a function of its massive molecular size, 500 million daltons to 100 GDa), blocking any transduction of signal, may occur. Its long-term effect may be due to low/high molecular weight mismatch correction resulting in TNFα-stimulated gene 6 protein modulation of the subclinical, regional inflammatory response. Dysregulation at the level of the extracellular neural matrix is stabilized, promoting a restoration of the normal immunoneural cross-talk, thereby negating what is believed to be the root cause for the development of chronic pain.15-18

Furthermore, any injury or insult to the nervous system may cause deafferentation pain (defined as “severe spontaneous pain in body parts distal to the injury despite reduced or no sensitivity to external noxious stimuli to that body part (hypoalgesia or analgesia)”19 as it represents a loss of information from the periphery to the brain. In the case presented, the nerve roots and spinal cord segments of the painful regions in question likely suffered deafferentation and neuropathic pain as a result of injury caused by the endometrial implants. It is this initial injury that likely initiated the cytokine cascade’s proinflammatory, pronociceptive state. For a complete discussion of these mechanisms of action in this regard, see the author’s previous report.13

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Step-by-Step Injection Technique to Target Endometriosis-Related Neuropathic Pelvic Pain