Perturbations in Neuroinflammatory Pathways Are Associated With a Worst Pain Profile in Oncology Patients Receiving Chemotherapy

J Pain. 2023 Jan;24(1):84-97. doi: 10.1016/j.jpain.2022.08.007. Epub 2022 Sep 15.


Unrelieved pain occurs in 55% of cancer patients. Identification of molecular mechanisms for pain may provide insights into therapeutic targets. Purpose was to evaluate for perturbations in neuroinflammatory pathways between oncology patients with and without severe pain. Worst pain severity was rated using a 0 to 10 numeric rating scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 192) and microarray (n = 197) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between None versus the Severe pain classes. In the RNA sequencing and microarray samples, 62.5% and 56.3% of patients were in the Severe pain class, respectively. Nine perturbed pathways were related to neuroinflammatory mechanisms (i.e., retrograde endocannabinoid signaling, gamma-aminobutyric acid synapse, glutamatergic synapse, Janus kinase-signal transducer and activator of transcription signaling, phagosome, complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, calcium signaling). First study to identify perturbations in neuroinflammatory pathways associated with severe pain in oncology outpatients. Findings suggest that complex neuroimmune interactions are involved in the maintenance of chronic pain conditions. Perspective: In this study that compared oncology patients with none versus severe pain, nine perturbed neuroinflammatory pathways were identified. Findings suggest that complex neuroimmune interactions are involved in the maintenance of persistent pain conditions.

Keywords: Cancer,chemotherapy; cytokines; gamma amino butyric acid; gene expression; glutamine; neuro-immune interactions; neuroinflammation.

MeSH terms

  • Cytokines
  • Humans
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Outpatients
  • Pain* / complications
  • Pain* / drug therapy
  • Signal Transduction


  • Cytokines