Sensory Phenotyping or Quantitative sensory testing-based phenotyping is a terminology used in the context of neuropathic pain management.

In a landmark randomised control trial by Demant et al, patients with peripheral neuropathic pain were classified by quantitative sensory testing (QST) into irritable receptor and non-irritable receptor phenotype.

The Irritable receptor phenotype group signifying sensory gain with preserved small fiber function was characterized clinically by mechanical and/or thermal allodynia, hyperalgesia and normal or near-normal thermal detection thresholds.

A substantially better response to oxcarbazepine (1800-2400 mg/day) was seen in this group with a number needed to treat (NNT) for 50 percent pain relief to be 3.9.

The mechanistic basis of this phenomenon can be explained on the basis of the underlying pathophysiology (that of peripheral sensitization mediated by ectopic nociceptor activity) which can be presumed to respond to sodium channel blockage.

The presence of evoked pain and intact thermal sensation can be used to select patients who might be expected to response to sodium channel blockers.

Similarly, Mechanical hyperalgesia (central sensitization) and deep, electrical or burning pain descriptors have been used as a marker of response to Pregabalin.

Cold and pin prick hyperalgesia (peripheral sensitization of TRPV1 receptors) has been identified as the phenotypic profile likely to respond to Capsaicin.

Response to capsaicin requires the TRPV1 Epidermal Nerve Fiber Density to be preserved. However the requirement is not merely the preservation of these nerve fibers, but in fact their role in pain generation. In conditions such as advanced diabetic neuropathy and chemotherapy-induced peripheral neuropathy characterized by severe intraepidermal nerve fiber depletion, capsaicin is expected to have limited utility only. Recent research such as the CAPSANEP trial and a study by Anand et al have shown evidence in favor of a disease-modifying effect of capsaicin on nerve fiber density (pointing towards its potential for healthier nerve fiber regeneration).

The phenomenon of defunctionalization is also specific to high concentration capsaicin (more than 5 percent w/w) where excessive calcium influx via TRPV1 receptors triggers chemoneurolysis.

Clustering of Neuropathic pain into three predominant phenotypes – mechanical hyperalgesia, thermal hyperalgesia and sensory loss is based upon underlying mechanisms of neuropathic pain generation and propagation and might act as a useful aid in selecting appropriate drug therapy.

The EMA Committee for Medicinal Products for Human Use has endorsed phenotypic stratification for the purpose of exploratory neuropathic pain trials, which might suggest future regulatory acceptance of this practice.

References

Demant DT, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain. 2014;155(11):2263-2273. doi:10.1016/j.pain.2014.08.014

Gewandter JS, et al. Predicting treatment response with sensory phenotyping in post-traumatic neuropathic pain. Pain Medicine. 2022;23(9):1559-1569. doi:10.1093/pm/pnac045 1

Arora V, et al. Fight fire with fire: neurobiology of capsaicin-induced analgesia for chronic pain. Pharmacology & Therapeutics. 2021;220:107743. doi:10.1016/j.pharmthera.2020.107743

Anand, P., Elsafa, E., Privitera, R., Naidoo, K., Yiangou, Y., Donatien, P., Gabra, H., Wasan, H., Kenny, L., Rahemtulla, A., & Misra, P. (2019). Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification. Journal of pain research, 12, 2039–2052. https://doi.org/10.2147/JPR.S213912

Sisignano, M., Rice, A. S. C., & Geisslinger, G. (2025). Topical Analgesics: Pharmacology and Clinical Applications. Anesthesiology, 143(5), 1371–1381. https://doi.org/10.1097/ALN.0000000000005579

Baron R, et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain. 2017;158(2):290-299. doi:10.1097/j.pain.0000000000000753

Vollert J, et al. Stratifying patients with peripheral neuropathic pain based on sensory profiles: algorithm and sample size recommendations. Pain. 2017;158(8):1441-1453. doi:10.1097/j.pain.0000000000000935

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