Pharmacological FMRI in the development of new analgesic compounds. by Schweinhardt, P, Bountra, C, Tracey, I

“…We are therefore optimistic that phFMRI will be used as a tool with high sensitivity and specificity for evaluating analgesic agents in early drug development and clinical studies.…”

Neuroimaging as a tool for pain diagnosis and analgesic development by Wartolowska, K, Tracey, I

“…Moreover, neuroimaging shows promising results for analgesic drug development and in characterizing different types of pain, bringing us closer to development of mechanism-based diagnoses and treatments for the chronic pain patient.…”

The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. by Bingel, U, Wanigasekera, V, Wiech, K, Ni Mhuircheartaigh, R, Lee, M, Ploner, M, Tracey, I

“…We investigated how divergent expectancies alter the analgesic efficacy of a potent opioid in healthy volunteers by using brain imaging. …”

Neuroimaging as a tool to investigate how cognitive factors influence analgesic drug outcomes. by Bingel, U, Tracey, I, Wiech, K

An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging. by Rogers, R, Wise, R, Painter, D, Longe, SE, Tracey, I

“…The aim of this study was to determine whether the analgesic effects of ketamine could be imaged. METHODS: Ketamine was administered to eight healthy volunteers with use of a target-controlled infusion to three predicted plasma concentrations: 0 (saline), 50 (subanalgesic), and 200 ng/ml (analgesic, subanesthetic). …”

Neuroimaging as a tool to investigate how cognitive factors influence analgesic drug outcomes by Bingel, U, Tracey, I, Wiech, K

Neuroimaging pain and analgesia mechanisms in experimental and chronic pain states by Waldman, S

“…Although it was not possible to show analgesic efficacy using behavioural outcomes, the presence of sedation in the active drug arm indicated a likely pharmacodynamic effect. …”

Dissociable neural mechanisms underlying the modulation of pain and anxiety? An FMRI pilot study by Wiech, K, Edwards, R, Moseley, G, Berna, C, Ploner, M, Tracey, I

“…In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. …”

Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain. by Lee, M, Wanigasekera, V, Tracey, I

“…There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. …”

Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. by Tracey, I

“…The findings have relevance for chronic pain states and other disorders, where abnormal functioning of crucial brain regions might affect analgesic outcome even in the normal therapeutic setting.…”

Neuroimaging in understanding chronic pain mechanisms and the development of new therapies by Wartolowska, K, Tracey, I

“…This chapter describes how brain imaging methods have been used in studies on pain, what neuroimaging tells us about the role of the central nervous system in pain processing, how being in constant pain affects the brain, and finally, how neuroimaging can be applied to improve the existing analgesic drugs and to discover new therapies. Neuroimaging makes it possible to study pain processing beyond the peripheral nervous system, at the supraspinal level, in a safe, noninvasive way, without interfering with neurophysiological processes. …”

The neural matrix of pain processing and placebo analgesia: Evidence from functional imaging by Tracey, I

“…Key regions that mediate the placebo effect include prefrontal cortices, anterior cingulate cortex (ACC) and brainstem structures, whereas the specific analgesic effects produced subsequent to a placebo response are mediated by a decreased activation in key pain processing brain regions, similar to that seen via pharmacological means. …”

Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain. by Wise, R, Williams, P, Tracey, I

“…Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. …”

Structural connectivity variances underlie functional and behavioral changes during pain relief induced by neuromodulation by Lin, R, Douaud, G, Filippini, N, Okell, T, Stagg, C, Tracey, I

“…Left dorsolateral prefrontal cortex (L-DLPFC) tDCS induced an analgesic effect, which was explained by reduced perfusion to posterior insula and thalamus. …”

Defining the Functional Role of NaV1.7 in Human Nociception by McDermott, L, Weir, G, Themistocleous, A, Segerdahl, A, Blesneac, I, Baskozos, G, Clark, A, Millar, V, Peck, L, Ebner, D, Tracey, I, Serra, J, Bennett, D

“…Loss-of-function mutations in NaV1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal approach, we investigated how NaV1.7 mutations lead to human pain insensitivity. …”

Amygdala activity contributes to the dissociative effect of cannabis on pain perception. by Lee, M, Ploner, M, Wiech, K, Bingel, U, Wanigasekera, V, Brooks, J, Menon, D, Tracey, I

“…On average, THC reduced the reported unpleasantness, but not the intensity of ongoing pain and hyperalgesia: the specific analgesic effect on hyperalgesia was substantiated by diminished activity in the anterior mid cingulate cortex. …”

Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. by Wise, R, Rogers, R, Painter, D, Bantick, S, Ploghaus, A, Williams, P, Rapeport, G, Tracey, I

“…Noxious thermal stimulation was combined with a single infusion and washout of remifentanil, a short-acting opioid analgesic agent. The temporal profile of the effect site concentration of remifentanil, estimated from a pharmacokinetic model, was incorporated into a linear model of the fMRI data. …”

Defining the neural correlates of pain and analgesia in health and disease by Mezue, M, Melvin Mezue

“…In a placebo-controlled study, we then demonstrated the improved sensitivity of fMRI above subjective reports in detecting the efficacy of a known analgesic as compared to an ineffective active compound in a small cohort. …”

Developing and characterising imaging biomarkers for pain and analgesia by Clarke, SEC

“…Functional magnetic resonance imaging (fMRI) is a highly valuable method to explore the neural basis for pain and also analgesic activity. This thesis combines these two research tools to develop and characterise neuroimaging biomarkers for pain and analgesia.…”

Disambiguating pharmacological mechanisms from placebo in neuropathic pain using functional neuroimaging by Wanigasekera, V, Wartolowska, K, Huggins, J, Duff, E, Vennart, W, Whitlock, M, Massat, N, Pauer, L, Rogers, P, Hoggart, B, Tracey, I

“…</p> <p><strong>Methods</strong><br/>We chronically administered pregabalin or tramadol (first-line and second-line analgesics, respectively), recommended for neuropathic pain, in 16 post-traumatic neuropathic pain patients. …”