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4 Articles in this Series
Complex Regional Pain Syndrome (CRPS): A Screening & Treatment Update
Facial Pain: Recognizing & Treating Trigeminal Neuralgia, Temporomandibular Disorders
Multiple Mini Interviews: The New Approach to Pain Fellow Recruitment
Neuropathic Pain: An Update on Practical Management Including Neurostimulation and Mechanism-Based Pharmacotherapy

Neuropathic Pain: An Update on Practical Management Including Neurostimulation and Mechanism-Based Pharmacotherapy

An Academy of Pain Medicine 2021 meeting highlight with Jijun Xu, MD, PhD, Jianguo Cheng, MD, PhD, and Charles E. Argoff, MD


Three leading experts provided an overview on the practical management of neuropathic pain at a 2021 AAPM virtual annual meeting session. Below are the highlights, covering identification and assessment of pain, neuromodulation treatment approaches, and mechanism-based pharmacological therapy.

Is It Neuropathic Pain? How Severe? A Look at Screening Assessments

Jijun Xu, MD, PhD, assistant professor of anesthesiology at the Cleveland Clinic, said that by definition, neuropathic pain is caused by a lesion or disease of the somatosensory nervous system and reminded participants that this type of pain can be central or peripheral. Thus, assessment is crucial.

Screening questionnaires can help clinicians identify whether a patient’s pain is neuropathic while assessment questionnaires can help determine the severity of the pain. Among the available tools:

  • Assessment of Neuropathic Symptoms and Signs (LANSS): asks 5 symptoms and 2 signs (0-24 scale, with scores below 12 likely nociceptive and over 12 likely neuropathic)
  • The Neuropathic Pain (NPQ): assesses degree of pain (10 symptoms, 2 signs, scores below zero not likely neuropathic; above zero likely neuropathic)
  • NPQ short form: uses a subset of 3 – numbness, tingling, and increased pain with touch (scores above zero likely neuropathic).
  • Douleur Neuropathique 4 (DN4): uses 7 symptoms, 3 signs (scores of 0 to 3 likely nociceptive pain, 4 or over likely neuropathic)
  • Neuropathic Pain Scale (NPS): 10 items assess pain
  • Neuropathic Pain Symptom Inventory (NPSI): patient self-report on degrees and description of pain

There are other questionnaires that can help to identify neuropathic pain in specific areas as well, including one focusing on back pain (see more resources in The Lancet Neurology). In one comparison, the DN4 won out for validity, noted the AAPM panelists.

“Assessment questionnaires are very good because they can be used to monitor patient outcome and to monitor the therapy effect,” said Dr. Xu,  “but they don’t include all sensory characteristics, for instance, numbness” The questionnaires cannot replace the clinical exam, however, which is fundamental to diagnose neuropathic pain, he added.

Laboratory Tests for Neuropathic Pain

Thus, Dr. Xu also discussed laboratory tests for neuropathic pain. Approaches include qualitative sensory testing, evoked potential, heat-evoked potential, laser-evoked potential or nerve conduction studies. The blink reflex measures a fiber in the trigeminal nerve system, useful to differentiate classic trigeminal neuralgia from other conditions. For diabetic neuropathy, clinicians may consider corneal confocal microscopy; this non-invasive test looks at nerve fiber damage in those with diabetes. In those with clinical signs of small fiber dysfunction, skin biopsy may be done.


Neurostimulation for Neuropathic Pain

In a second talk on neuropathic pain, Jianguo Cheng, MD, PhD, professor and director of the Cleveland Clinic Multidisciplinary Pain Medicine Fellowship Program, talked about neuromodulation as a treatment approach. He pointed to practice recommendations made by the NeuPSIG experts, French pain experts,and others, but noted that most of them, including spinal cord stimulation (SCS) for CRPS Type 1, are weak.

Dr. Cheng highlighted other data:

  • n a review article, both Drs. Cheng and Xu discuss how advances in SCS for chronic pain management have significantly improved by the development of high frequency (HF-10kHz) stimulation, burst stimulation, and dorsal root ganglion (DRG) stimulation
  • This study by Rigoard et al demonstrates that SCS for failed back surgery syndrome is effective
  • Some data shows that closed-loop SCS may be better than open-loop
  • For lower extremity CRPS, DRG is FDA approved
  • Other promising data show that peripheral nerve stimulation, brain stimulation and intrathecal therapy may also help neuropathic pain.

Looking ahead, Dr. Cheng said, “Neurostimulation has an increasing role in refractory NP [neuropathic pain].”

Pharmacologic Therapy for Neuropathic Pain

Charles Argoff, MD, professor of neurology at Albany Medical College and director of the comprehensive pain center at Albany Medical Center, focused on mechanism-based pharmacological therapy for neuropathic pain.

He opened his AAPM talk by acknowledging that “We are scratching the surface” of how to treat neuropathic pain with a totally mechanism-based approach, adding for context, “I am going to focus most on the mechanism of the pharmacological agent used to treat NP.”

The list of current pharmacotherapy options for managing neuropathic pain is long – among those shared by Dr. Argoff:

  • TCA or SNRI antidepressants
  • Sodium channel blocker anticonvulsants
  • CA2+ (calcium)-modulating anticonvulsants
  • Tramadol
  • Opioids
  • TRPV1 topical agents
  • local anesthetic topic agents
  • botulinum toxin

Treating neuropathic pain by a mechanism approach is not akin to treating an infection, however, said Dr. Argoff. When considering medications, for instance, a substance like ketamine may attenuate central sensitization via NMDA receptor antagonism. And while ketamine has been helpful for some patients with CRPS, it’s not as helpful for post-herpetic neuralgia (PHN). And sodium channel blockers such as lidocaine likely act on peripheral pain generating mechanisms, he added.

According to Dr. Argoff, recent approaches to stratify patients based on a specific underlying mechanism may lead to mechanism-based treatment of neuropathic pain in the future. Active investigations are ongoing, including the phenotyping and subgrouping of patients. There are mixed results and still no clear takeaways, he concluded. “Overall, mechanism-based pharmacological therapy for NP is in development.”

Clinical Takeaways

For neuropathic pain assessment, Dr. Xu told PPM after the session: “Practically, I would recommend use of the DN4 questionnaire to help identify whether the patient has a neuropathic component of the pain.” It is the questionnaire often singled out by some experts.

While some research has shown that neurostimulation beats out conventional treatment for neuropathic pain, more studies are needed and underway. The latter is true for mechanism-based pharmacotherapy as well.  


No disclosures reported on speakers’ AAPM slide decks.


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