Oxaliplatin causes increased offset analgesia during chemotherapy - a feasibility study.

OBJECTIVES: Offset analgesia (OA) is the phenomenon where the perceived pain intensity to heat stimulation disproportionally decreases after a slight decrease in stimulation temperature. The neural mechanisms of OA are not fully understood, but it appears that both peripheral and central temporal filtering properties are involved. Chemotherapy with oxaliplatin often causes acute peripheral sensory neuropathy, and manifests primarily as a cold induced allodynia. The aim of this exploratory patient study was to investigate if OA was affected by the neurotoxic effects of adjuvant oxaliplatin treatment. METHODS: OA was assessed in 17 colon cancer patients during 12 cycles of adjuvant oxaliplatin treatment. The OA response was estimated as the decrease in pain intensity caused by a temperature decrease from 46 °C to 45 °C. Changes in the OA during the treatment period was estimated using a mixed linear model and corrected for multiple comparisons by Sidak's test. RESULTS: OA was increased significantly when assessed before the 2nd, 3rd, 5th, 6th, 9th, and 10th treatment cycle compared to the first (baseline) treatment (p<0.05). CONCLUSIONS: OA is generally decreased in persons suffering from chronic pain or peripheral neuropathy as compared to healthy controls. But in the present study, OA increased during chemotherapy with oxaliplatin. The underlying mechanism of this unexpected increase should be further explored.

New diagnostic measures of oxaliplatin-induced peripheral sensory neuropathy.

OBJECTIVE: Oxaliplatin-induced peripheral neuropathy (OIPN) is an unwanted side effect of oxaliplatin chemotherapy treatment. OIPN manifests in an acute phase that lasts a few days after injection and a persistent phase that may become chronic. Currently, there is no consensus about a clinically applicable, quantitative, and objective measure of OIPN. METHODS: Seventeen patients treated with oxaliplatin containing adjuvant chemotherapy for stage III colon cancer, but otherwise healthy, were tested with six quantitative sensory tests (QST) and five large fibre perception threshold tracking (PTT) measures (quantified by, e.g., rheobase and electrotonus threshold) one hour before each of the 12 chemotherapy cycles given at two weeks' intervals. These measures were repeated at 3, 6, and 12-month follow-ups. The temporal development of OIPN assessed by the Common Terminology Criteria for Adverse Events (CTCAE) scale, QST, and PTT measures was calculated by linear regression. RESULTS: The CTCAE score showed a tri-phasic increase during the treatment and remained increased during the follow-up. The vibration threshold (R = 0.25, p<0.001), the cold pain threshold (R = 0.17, p = 0.02), and the rheobase (R = 0.28, p < 0.001) increased during treatment, whereas the cold detection threshold (R=-0.16, p = 0.002) decreased. The cold pain threshold and the rheobase remained increased, and the cold detection and heat pain threshold remained decreased during follow-up. CONCLUSIONS: Increased cold pain sensitivity and decreased large fibre sensitivity (increased rheobase) correlate to the persistent OIPN, whereas the CTCAE score assesses both acute and persistent OIPN. Furthermore, the novel PTT method assessed the nerve excitability changes caused by the oxaliplatin.