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.…”

Potent, selective adenosine Al agonists as potential analgesics by Beswick, P, Bountra, C, Clayton, N, Collins, S, Cousins, R, Eldred, C, Naylor, A, Sheehan, M, Spalding, D

The use of locomotor activity equipment to assess analgesic and anti-inflammatory activity by Thompson, S, Clayton, N, Oakley, I, Bountra, C

Lost but making progress--Where will new analgesic drugs come from? by Borsook, D, Hargreaves, R, Bountra, C, Porreca, F

“…The paucity of new drugs successfully reaching the clinic calls for a reassessment of current analgesic drug discovery approaches. Many points early in the discovery process present significant hurdles, making it critical to exploit advances in pain neurobiology to increase the probability of success. …”

The effects of ibuprofen and the neurokinin-1 receptor antagonist GR205171A on Fos expression in the ferret trigeminal nucleus following tooth pulp stimulation. by Worsley, M, Clayton, N, Bountra, C, Boissonade, F

“…The aim of this study was to establish the ability of this model to predict analgesic efficacy in clinical studies of inflammatory pain. …”

Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors. by Beswick, P, Bingham, S, Bountra, C, Brown, T, Browning, K, Campbell, I, Chessell, I, Clayton, N, Collins, S, Corfield, J, Guntrip, S, Haslam, C, Lambeth, P, Lucas, F, Mathews, N, Murkit, G, Naylor, A, Pegg, N, Pickup, E, Player, H, Price, H, Stevens, A, Stratton, S, Wiseman, J

“…Several examples of the series, in addition to possessing favourable pharmacokinetic profiles and analgesic activity in vivo, have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.…”

An NMR-based metabolic profiling study of inflammatory pain using the rat FCA model by Connor, S, Gray, R, Hodson, M, Clayton, N, Haselden, J, Chessell, I, Bountra, C

“…Therefore, it would be advantageous to identify a biological marker which is sensitive to pain pathology and modulated by an efficacious analgesic/anti-inflammatory agent. The present study highlights several metabolites present in urine that are modulated from basal levels by pain and inflammation induced following hindpaw injection of Freund's Complete Adjuvant. …”

Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. by Anand, U, Otto, W, Sanchez-Herrera, D, Facer, P, Yiangou, Y, Korchev, Y, Birch, R, Benham, C, Bountra, C, Chessell, I, Anand, P

“…Animal models suggest that they act mainly via non-neuronal cells, possibly inhibition of inflammatory cells in the periphery or CNS, or via release of beta-endorphin; however, the clinical relevance and mechanism of analgesic action is uncertain. Here, we demonstrate colocalisation of CB2 with CB1 and the capsaicin receptor TRPV1 in human dorsal root ganglion (DRG) sensory neurons and increased levels of CB2 receptors in human peripheral nerves after injury, particularly painful neuromas. …”

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: mechanisms underlying hypoalgesia in Buruli ulcer by Anand, U, Sinisi, M, Fox, M, Macquillan, A, Quick, T, Korchev, Y, Bountra, C, McCarthy, T, Anand, P

“…In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. …”

Use of the novel contact heat evoked potential stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fib... by Atherton, D, Facer, P, Roberts, K, Misra, V, Chizh, B, Bountra, C, Anand, P

“…Although further evaluation is required, the technique shows potential clinical utility to differentiate neuropathy from other chronic pain states, and provide a biomarker for analgesic development. </p> …”

Plasticity of TTX-sensitive sodium channels PN1 and brain III in injured human nerves. by Coward, K, Aitken, A, Powell, A, Plumpton, C, Birch, R, Tate, S, Bountra, C, Anand, P

“…PNI and Brain III are distinct targets for novel analgesics.…”

Expression of the sodium channel beta3 subunit in injured human sensory neurons. by Casula, M, Facer, P, Powell, A, Kinghorn, I, Plumpton, C, Tate, SN, Bountra, C, Birch, R, Anand, P

“…Targeting beta3 interactions with key alpha-subunits, particularly Nav1.3 and Nav1.8, may provide novel selective analgesics.…”

Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in injured human sensory neurons. by Coward, K, Jowett, A, Plumpton, C, Powell, A, Birch, R, Tate, S, Bountra, C, Anand, P

“…Our results suggest that alpha- and beta-subunits share common regulatory mechanisms, but present distinct targets for novel analgesics.…”

The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. by Anand, U, Otto, W, Casula, M, Day, N, Davis, J, Bountra, C, Birch, R, Anand, P

“…NTFs thus increase size, elevate TRPV1 levels and enhance capsaicin responses in cultured human DRG neurons; these changes may relate to pathophysiology in disease states, and provide an in vitro model to study novel analgesics.…”

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models. by Wilson, A, Medhurst, S, Dixon, C, Bontoft, N, Winyard, L, Brackenborough, K, De Alba, J, Clarke, C, Gunthorpe, M, Hicks, G, Bountra, C, McQueen, D, Chessell, I

“…A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). …”