Conditioned Pain Modulation and Cold Conditioning Stimulus Among Patients With Chronic Upper Limb Neuropathy

Peripheral Neuropathy pain in elderly patient
The researchers’ aim in this study was to compare subjects with and without neuropathic pain, all after operative nerve repair in the upper extremities.

Individuals with chronic painful neuropathy were able to withstand longer periods of cold conditioning stimulus (CS) but had a longer recovery time compared with patients who had chronic nonpainful neuropathy. These findings from a cross-sectional study were published in Pain Reports.

Patients (N=131) with a definitive upper extremity nerve injury who underwent surgery were recruited from the Multidisciplinary Pain Center at Uppsala University Hospital in Sweden. Participants responded to extensive questionnaires about demographics and underwent pain assessment and thermal quantitative sensory testing.

Patients, who were stratified by neuropathic pain (n=69) and nonpainful neuropathy (n=62), had a median age of 48 (range, 20-86) and 49 (range, 19-83) years and 76.9% and 63.1% were men, respectively.

The cohort of patients with painful neuropathy had received their operation more recently (P <.001), had greater pain intensity (P <.0001), had higher Leeds Assessment of Neuropathic Symptoms and Signs scores (P <.0001) and Quick Disabilities of the Arm, Shoulder, and Hand scores (P <.001), and had lower 36-Item Short-Form Health Survey scores (P <.001).

During the standard bedside examination, patients in the cohort with painful neuropathy had gain of function according to pinprick hyperalgesia (P <.0001), dynamic mechanical allodynia (P <.0001), and cold hyperesthesia (P =.0009, but loss of function to warm sensation (P =.03) compared with patients in the nonpainful neuropathy group.

Comparing patients’ injured and healthy sides, thermal differences (P <.0001), increased mechanical detection thresholds (P <.001), and decreased pressure pain thresholds (P <.05) were observed.

Conditioned pain modulation was observed among 82% of the patients in the painful neuropathy and 77% of the patients in the nonpainful neuropathy groups. No significant group effect for conditioned pain modulation was observed (P >.05).

The majority of patients in the painful (66%) and nonpainful (54%) neuropathy groups could sustain cold exposure for 60 seconds; however, pain lasted longer among the patients with painful neuropathy (42 vs 19 seconds; P <.0001) after CS, corresponding with an increased risk for later pain recovery (odds ratio [OR], 1.8; 95% CI, 0.97-3.29).

This study was conducted among a subset of patients with neuropathy — those with wrist or hand nerve lesions who underwent surgery — and therefore the results may not be generalizable to other types of neuropathy.

These data indicated patients with painful or nonpainful neuropathy had similar conditional pain modulation and patients with painful neuropathy were able to sustain CS longer but had increased recovery time from the resultant pain. These data may indicate CS may be a method for studying endogenous pain among patients with painful neuropathy.


Miclescu A, Essemark M, Astermark M, et al. Prolonged time of after-sensation after experimental pain stimuli despite efficient conditioned pain modulation in patients with chronic neuropathic pain after traumatic nerve injuries in upper extremity. Pain Rep. 2021;6(1):e908. doi:10.1097/PR9.0000000000000908