12–14 The aforementioned neurotransmission construct of the CPM response suggests augmentation of the descending inhibition leading to anti-nociception by increase of synaptic levels of noradrenaline and serotonin.15 Figure 1 An Example of a Conditioned Pain Modulation (CPM) Test Protocol. Pain facilitation is measured using the temporal summation (TS) protocol, where a series of identical stimuli is given and NPS obtained along the series. The common response is an increase in pain ratings along the series, representing the physiological phenomenon of wind-up—the Inhibitors,research,lifescience,medical sensitization of nociceptors

in response to intense activation. Inhibitors,research,lifescience,medical TS represents neurophysiologic processes induced by excessive activation of N-methyl-D-aspartate (NMDA) receptors of the second-order neurons, in response to intensive nociceptive input, and its expression depends on flow of Ca2+ ions into the neuronal cytoplasm.16 Thus, neuronal wind-up subsequent to the enhanced Ca2+ influx-dependent release of glutamate, norepinephrine, and Inhibitors,research,lifescience,medical substance P may serve as a target for the agents that are expected to diminish this central neuronal hyperexcitability. In other words, agents that target the Ca2+ influx may reduce enhanced TS and alleviate pain. These dynamic tests induce

a process of modulation and are believed to reflect the “real-life” modulation exerted by patients when exposed to clinical pain. There is a large body of data showing differences between pain modulation states in patients suffering from idiopathic and other pain syndromes as compared to the healthy controls: Inhibitors,research,lifescience,medical Fibromyalgia. Various pain modalities applied for the noxious conditioning MK518 stimulation, by ischemic, contact heat, or cold noxious water, were non-efficient in increasing pain thresholds or reducing experimental supra-threshold pain magnitudes.17–19 Evidence for abnormal

Inhibitors,research,lifescience,medical TS includes enhanced pain summation in response to repeated heat taps and repeated muscle taps delivered at a remote body area, as well as prolonged and enhanced painful after-sensations. Moreover, magnitudes of enhanced after-sensations were predictive of patients’ ongoing clinical pain.20–22 Irritable bowel syndrome. The experimentally induced visceral Carnitine palmitoyltransferase II or cold water pain was not effective in reducing ongoing rectal pain or the perception of noxious heat.23–25 Headache. Facilitation, rather than normally occurring inhibition, of nociceptive reflex was observed in migraine patients conditioned by noxious cold water.26 In line with this, in chronic tension-type headache patients, conditioning by tonic muscle pain failed to reduce the responses to electrical pain as recorded by somatosensory event-related potentials over the scalp.