Opioid treatment of experimental pain activates nuclear factor-κB

Abstract

Objective: To determine the independent and combined effects of pain and opioids on the activation of an early marker of inflammation, nuclear factor-κB (NF-κB).

Design: NF-κB activation was compared within-subjects following four randomly ordered experimental sessions of opioid-only (intravenous fentanyl 1 μg/kg), painonly (cold-pressor), opioid + pain, and a resting condition.

Setting: University General Clinical Research Center.

Participants: Twenty-one (11 female) healthy controls.

Interventions: Following exposure to treatment (fentanyl administration and/or cold-pressor pain), blood samples for NF-κB analysis were obtained.

Main outcome measures: Intracellular levels of activated NF-κB, in unstimulated and stimulated peripheral blood mononuclear cells at 15 and 30 minutes.

Results: Neither pain nor opioid administration alone effected NF-κB levels in cell populations; however, the combination of treatments induced significant increases of NF-κB in stimulated peripheral blood mononuclear cell, lymphocytes, and monocytes.

Conclusions: The combination of acute pain with opioids, as occurs in clinical situations, activates a key transcription factor involved in proinflammatory responses.

Figures

Figure 1

Levels of intranuclear activated NF-κB induced in stimulated cells. Mean ± SD of increases in mean fluorescent intensity (MFI) compared to unstimulated cells (MFI delta = MFI stimulated cells – MFI unstimulated cells), adjusted for baseline MFI delta values, in (a) peripheral blood mononuclear cells (PBMC). Pain vs opioid + pain, p = 0.034. Opioid vs opioid + pain, p = 0.016. (b) Monocytes. Pain vs opioid + pain, p = 0.044. Opioid vs opioid + pain, p = 0.004. (c) Lymphocytes. Pain vs opioid + pain, p = 0.034. Opioid vs opioid + pain, p = 0.018. Control vs opioid + pain, p = 0.045. p values shown are for the indicated pairwise comparison by ANOVA across time points.