# Application of a Nociceptive Test Battery to Assess Potential Synergy between Two Analgesics in Healthy Subjects

## TL;DR

This study tests a combination of pregabalin and morphine in healthy volunteers to see if it provides better pain relief with fewer side effects than either drug alone.

## Contribution

The study introduces a validated nociceptive test battery to evaluate opioid-sparing analgesic combinations in healthy subjects.

## Key findings

- The pregabalin–morphine combination significantly increased pain tolerance on multiple tests.
- The combination caused minimal additional CNS side effects compared to monotherapy and placebo.

## Abstract

Chronic pain management remains a major challenge due
to the risks
associated with conventional treatments, such as opioids and NSAIDs,
which carry significant risks, including addiction, tolerance, and
adverse side effects, particularly with prolonged use. Combining opioid
with nonopioid drugs offer a potential solution, as it may minimize
opioid-related side effects by reducing the required opioid dose.
We performed a study to compare the analgesic effects and safety of
a pregabalin–morphine combination to each drug alone and placebo
in healthy volunteers. A randomized, double-blind, placebo-controlled
crossover design was used, with subjects receiving 300 mg of pregabalin
combined with 3 and 7 mg of morphine, morphine only, pregabalin only,
or a double placebo. Analgesic effects and CNS side effects were assessed
up to 10 h postdose using nociceptive and neurocognitive test batteries.
Results demonstrated that the pregabalin–morphine combination
significantly increased pain tolerance compared to either drug alone
on several pain tests (cold pressor, electrical burst, electrical
stair, and pressure pain) with only minimal additional CNS side effects
compared to monotherapy and placebo. This study indicates that validated
nociceptive and CNS test batteries were suitable to assess the potential
of opioid–sparing combination therapies in an experimental
setting.