HEFT Repository

Disambiguating pharmacological mechanisms from placebo in neuropathic pain using functional neuroimaging.

Wanigasekera, V and Wartolowska, K and Huggins, J P and Duff, E P and Vennart, W and Whitlock, M and Massat, N and Pauer, L and Rogers, P and Hoggart, B and Tracey, I (2018) Disambiguating pharmacological mechanisms from placebo in neuropathic pain using functional neuroimaging. British journal of anaesthesia, 120 (2). pp. 299-307. ISSN 1471-6771. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

Full text not available from this repository.
Official URL: http://bjanaesthesia.org/article/S0007-0912(17)540...

Abstract

BACKGROUND

A lack of objective outcome measures and overreliance on subjective pain reports in early proof-of-concept studies contribute to the high attrition of potentially effective new analgesics. We studied the utility of neuroimaging in providing objective evidence of neural activity related to drug modulation or a placebo effect in a double-blind, randomized, placebo-controlled, three-way crossover trial.

METHODS

We chronically administered pregabalin or tramadol (first-line and second-line analgesics, respectively), recommended for neuropathic pain, in 16 post-traumatic neuropathic pain patients. We measured subjective pain reports, allodynia-evoked neural activity, and brain resting state functional connectivity from patients during the three sessions and resting state data at baseline from patients after washout of their current medication. All data were collected using a 3 T MRI scanner.

RESULTS

When compared with placebo only, pregabalin significantly suppressed allodynia-evoked neural activity in several nociceptive and pain-processing areas of the brain, despite the absence of behavioural analgesia. Furthermore, placebo significantly increased functional connectivity between the rostral anterior cingulate and the brainstem, a core component of the placebo neural network.

CONCLUSIONS

Functional neuroimaging provided objective evidence of pharmacodynamic efficacy in a proof-of-concept study setting where subjective pain outcome measures are often unreliable. Additionally, we provide evidence confirming the neural mechanism underpinning placebo analgesia as identified in acute experimental imaging studies in patients during the placebo arm of a clinical trial. We explore how brain penetrant active drugs potentially interact with this mechanism.

CLINICAL TRIAL REGISTRATION

NCT0061015.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WL Nervous system. Neurology > WL800 Pain
WO Surgery > WO500 Anaesthesia
Divisions: Clinical Support > Anaesthetics
Related URLs:
Depositing User: Mrs Caroline Tranter
Date Deposited: 13 Feb 2018 14:35
Last Modified: 13 Feb 2018 14:35
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1594

Actions (login required)

View Item View Item