Biomarkers for Prediction of Analgesic Efficacy in Knee OA.

The investigators propose a framework of interrelations between patient's pain modulation profile (PMP) and the drug's mode of action (MOA) based on two principles: (1) 'fix the dysfunction', relevant for drugs whose main mode of action is to modulate central pain processing; the more the dysfunctional the better the modulating drug efficacy. For example, patients with pro-nociceptive PMP due to reduced endogenous pain inhibition, as expressed by less efficient CPM will benefit from drugs that fix this dysfunction such as SNRIs, relative to patients whose pain inhibitory capacity is well functioning. Thus, for the modulating drugs, pro-nociceptivity predicts better efficacy. (2) 'bear with the dysfunction', relevant for drugs which are mostly non-modulating, acting mainly in the periphery; the more dysfunctionalת the less the non-modulating drug efficacy. This is since efficacy is limited by the dysfunctional modulation system, despite the drug's MOA-like reduction of peripheral pain mediators. Thus, for the non-modulating drugs, for example NSAIDs, pro-nociceptivity predicts less good efficacy. The likely protocol suggests that patients with anti-nociceptive PMP should be treated primarily by non-modulating drugs, while pro-nociceptive ones should be given modulating drugs.

EEG is an additional source of relevant data on brain pain processing. Being objective and stable along time, EEG based parameters are, thus, very attractive candidates to be useful biomarkers for prediction of analgesia efficacy.

This study will focus on the patients with painful knee osteoarthritis.

The aims of this study are:

1. To identify psychophysical and neurophysiological biomarkers that can serve as predictors of response to analgesic pain modulating and non-pain modulating drugs. 2. To establish a conceptual framework of individualized pain therapy based on inter-relations between patient's parameters of pain modulation and drugs' mode of action.