Oral opioid use alters DNIC but not cold pain perception in patients with chronic pain - New perspective of opioid-induced hyperalgesia

Opioids can elicit unexpected changes in pain sensitivity, known as opioid-induced hyperalgesia (OIH). The aim of this study was to explore whether OIH exists in patients with chronic pain treated with oral opioids (OP) versus non-opioid (NOP) analgesics. The sensitivity to cold pain and the magnitude of diffuse noxious inhibitory control (DNIC) were evaluated in 73 OP and 37 NOP treated patients. Pain threshold, intensity and tolerance in response to the cold pressor (1 °C) were measured. DNIC was tested by co-administrating conditioned heat stimulation (47 °C) to the left forearm and a conditioning stimulation of 12 °C for 30 s to the right hand. The results showed no differences between the two groups in any of the cold pain measures. In contrast, the magnitude of DNIC was significantly larger in the NOP than in the OP treated patients (p = 0.003). A gender based analysis showed a significant difference in DNIC between OP and NOP treated men only. However, a mixed model ANOVA demonstrated a significant effect of treatment (OP versus NOP) (F = 5.928, p = 0.017) rather than gender on DNIC. A regression analysis showed that opioid dosage and treatment duration had a significant negative effect on the magnitude of DNIC in OP treated men (β = -2.175, p = 0.036 and β = -2.061, p = 0.047, respectively). In conclusion, oral opioids usage for the treatment of chronic pain does not result in abnormal sensitivity to cold pain, but seems to alter pain modulation. The use of 'advanced' psychophysics tests such as evaluation of DNIC can help understanding the phenomenon of OIH.