Starting strong: A descending analgesic dosing scheme enhances pain relief compared to a conventional ascending dosing scheme
- 1University Medical Center Hamburg-Eppendorf
Abstract
Managing pain while minimizing opioid-related harm remains a central clinical challenge. Enhancing drug-related placebo effects has been proposed as one strategy for reducing opioid consumption, yet current dosing guidelines which recommend starting analgesic treatment at a low dose and titrating upward may inadvertently generate negative treatment expectations, since initial drug encounters are often associated with minimal pain relief. This study tested whether the inverse approach of a descending dosing scheme that starts with a strong analgesic dose more effectively enhances placebo-related analgesia than the conventional ascending scheme. Eighty-two healthy participants underwent a heat pain paradigm involving a sham analgesic treatment delivered at three different efficacy levels (low, medium, high). Participants were randomly assigned to a descending (high-to-low) or ascending (low-to-high) treatment-history sequence before receiving an identical, medium-intensity treatment during a subsequent test phase. The descending group showed significantly greater pain relief during the test phase than the ascending group, despite receiving identical treatment. These findings suggest that initiating analgesic treatment with a high, effective dose can amplify placebo-related analgesia relative to conventional dosing schemes, offering a potential strategy for reducing cumulative opioid use without compromising pain relief.
Related
- Behavioral discrimination between ascending versus descending FM sweeps lowers the thresholds of auditory brainstem responses in good learner rats
- Aortopulmonary Fistula Complicating a Ruptured Infected Proximal Descending Thoracic Aortic Pseudoaneurysm.
- Associations of age, sex, and bicuspid aortic valve with biaxial mechanical properties and circumferential residual stress in ascending thoracic aortic aneurysm
- Ascending Inputs to Inferior Colliculus Subdivisions Reveal Pathway-Specific Hybrid Organization in the External Cortex
- Synaptic placement reflects shared input in Drosophila descending neurons
BibTeX
@misc{mintah2026starting,
title = {{Starting strong: A descending analgesic dosing scheme enhances pain relief compared to a conventional ascending dosing scheme}},
author = {M. Mintah and J. Daunizeau and A. Tinnermann},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.10.758177},
url = {https://www.biorxiv.org/content/10.64898/2026.10.10.758177v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Starting strong: A descending analgesic dosing scheme enhances pain relief compared to a conventional ascending dosing scheme
AU - M. Mintah
AU - J. Daunizeau
AU - A. Tinnermann
PY - 2026
DA - 2026/10/10
PB - bioRxiv
DO - 10.64898/2026.10.10.758177
UR - https://www.biorxiv.org/content/10.64898/2026.10.10.758177v1
AB - Managing pain while minimizing opioid-related harm remains a central clinical challenge. Enhancing drug-related placebo effects has been proposed as one strategy for reducing opioid consumption, yet current dosing guidelines which recommend starting analgesic treatment at a low dose and titrating upward may inadvertently generate negative treatment expectations, since initial drug encounters are often associated with minimal pain relief. This study tested whether the inverse approach of a descending dosing scheme that starts with a strong analgesic dose more effectively enhances placebo-related analgesia than the conventional ascending scheme. Eighty-two healthy participants underwent a heat pain paradigm involving a sham analgesic treatment delivered at three different efficacy levels (low, medium, high). Participants were randomly assigned to a descending (high-to-low) or ascending (low-to-high) treatment-history sequence before receiving an identical, medium-intensity treatment during a subsequent test phase. The descending group showed significantly greater pain relief during the test phase than the ascending group, despite receiving identical treatment. These findings suggest that initiating analgesic treatment with a high, effective dose can amplify placebo-related analgesia relative to conventional dosing schemes, offering a potential strategy for reducing cumulative opioid use without compromising pain relief.
ER -