Patients presenting with acute neuropathic pain represent a significant diagnostic challenge. As such, diagnostic criteria should reflect the mechanistic understanding of this pain as well as provide a framework for research and treatment of complex acute neuropathic pain conditions.

Through a partnership of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), the US Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM), an expert working group collaboratively developed the ACTTION-APS-AAPN Pain Taxonomy (AAAPT) for acute pain, which was published in Pain Medicine.

5 Dimensions of Pain

The AAAPT classifies acute pain across 5 dimensions: core criteria, common features, modulating factors, impact and functional consequences, and putative pathopsychological pain mechanisms. In brief, the overarching characteristics of each of these dimensions are as follows:


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Core criteria: Defined by unpleasant sensory and emotional experiences associated with either actual or potential tissue damage, or described in the terms of such damage; pain that occurs within 30 days of an inciting incident that causes neurologic injury; pain located in a “neuroanatomically plausible distribution” that is consistent with neurologic injury; and pain associated with at least 1 physical examination finding of either sensory deficit or sensory gain (eg, allodynia, hypoalgesia, hyperalgesia).

Common features: Pain may originate anywhere in the body. It is typically described using the following terms: burning, shooting, tingling, electric, or pins and needles.

Modulating factors: Pain may be modulated by the patient’s age or immune function, the presence of other nervous system diseases such as multiple sclerosis or Parkinson disease, genetic polymorphisms, or psychosocial factors.

Impact and functional consequences: Pain is associated with poor physical functioning and interferes with emotional and social well-being, resulting in a diminished quality of life.

Putative mechanisms: This category includes ectopic nervous system activity, peripheral and central sensitization, loss of descending inhibition, and neuroimmune interactions; influences are likely genetic or epigenetic.

The working group then applied the AAAPT criteria to 3 specific conditions that most aptly “exemplify acute neuropathic pain” and demonstrate its range: acute herpes zoster-related neuropathic pain, acute chemotherapy-induced neuropathic pain, and acute neuropathic pain following limb amputation. Diagnostic criteria for each condition across the 5 identified acute neuropathic pain dimensions are described briefly below.

Core criteria includes acute or subacute herpetic neuralgia, typically several days prior to the appearance of a dermatomal rash, at the time when the rash appears, or shortly afterwards (within 30 days for acute or within 30 to 119 days for subacute), as well as one positive or negative sensory sign in the affected dermatome. No other conditions could better explain the pain.

Pain may be described as stimulus-independent ongoing or intermittent, or stimulus evoked, and dysesthesias or paresthesias may also be present.

Modulating factors include age, rash severity, presence of painful prodrome, and immune status. Functional consequences range from difficulty with sleep and other activities of daily living to depression and interference with social well-being, as well as a decreased health-related quality of life.

This pain may arise from neural injury due to herpes zoster reactivation. A combination of mechanisms may be responsible for individual patient symptoms.

Core criteria include a history of receiving a neurotoxic chemotherapeutic agent, pain that occurs within 30 days of the administration of this agent, pain distribution neuroanatomically consistent with a neurologic lesion, pain with at least one positive or negative sensory sign, and no other condition that could better explain the pain. Pain may be present in upper and/or lower extremities.

Pain may be modulated by the patient’s comorbid medical conditions, immune status, social and demographic factors, lifestyle, and genetics. Functional consequences include difficulties with activities of daily living, interference with emotional and social well-being, and a decrease in the dose or total cessation of chemotherapy.

Putative mechanisms include damage to neuronal DNA, mitochondria, endoplasmic reticulum, and cell bodies in the dorsal root ganglia axons, as well as alterations in ion channels leading to ectopic activity.

Core criteria include a history of amputation, pain occurring within 30 days of amputation, and pain that is perceived in either the amputated limb or the stump of the amputated limb; no other diagnosis better explains this pain. Other common features include telescoping or a sensation of limb shortening in phantom limb pain and spontaneous stump movements in residual limb pain — both of which tend to decrease over time.

Pain may be modulated by psychological factors such as depression, anxiety, and post-traumatic stress disorder (PTSD), the incidence and severity of preamputation pain, and perioperative analgesia. Functional consequences include decreased patient satisfaction, reduced quality of life, increased requirements for postoperative medication, and a progression to chronic postamputation pain.

Putative mechanisms include damage from severing peripheral nerves that leads to ectopic discharge, central sensitization, and both spinal and supraspinal reorganization.

Framework Needed

“Acute neuropathic pain is…temporally distinct from but closely related to chronic neuropathic pain,” the researchers wrote. “The proposed AAAPT diagnostic criteria for acute neuropathic pain have been developed to distinguish it from both chronic neuropathic pain and acute non-neuropathic pain, reflecting our current understanding of its unique mechanisms and clinical features.”

Additional studies, they added, on the mechanisms, pathophysiology, and epidemiology of acute neuropathic pain are necessary to “establish the reliability and validity of the proposed diagnostic criteria.”

“This proposed framework for understanding acute neuropathic pain in the context of other pain conditions may allow clinicians and researchers to improve how we prevent, diagnose, and manage acute neuropathic pain,” the researchers concluded.

Reference

Doshi TL, Dworkin RH, Polomano RC, et al. AAAPT diagnostic criteria for acute neuropathic pain. Pain Med. Published online February 12, 2021. doi:10.1093/pm/pnaa407