A single-center, randomized, double-blind, active, and placebo-controlled study of KAI-1678, a novel PKC-epsilon inhibitor, in the treatment of acute postoperative orthopedic pain

Pain Medicine (United States)

Volumn 14, Issue 6, 2013, Pages 916-924

  Moodie, John E ^a   Bisley, Eileen J ^a   Huang, Saling ^b   Pickthorn, Karen ^b   Bell, Gregory ^b,c  

^a Waikato Clinical Research   (New Zealand)

^b KAI Pharmaceuticals   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Acute pain; Analgesic; Epsilon protein kinase C inhibitor; KAI 1678; Postoperative orthopedic pain

Indexed keywords

ANALGESIC AGENT; KAI 1678; KETOROLAC; PROTEIN KINASE C INHIBITOR; SODIUM CHLORIDE; UNCLASSIFIED DRUG;

ADULT; ANALGESIC ACTIVITY; ARTICLE; BONE PAIN; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ERYTHEMA; FEMALE; HIP ARTHROPLASTY; HUMAN; KNEE ARTHROPLASTY; MAJOR CLINICAL STUDY; MALE; PAIN ASSESSMENT; PHASE 2 CLINICAL TRIAL; POSTOPERATIVE ANALGESIA; POSTOPERATIVE PAIN; RANDOMIZED CONTROLLED TRIAL; VISUAL ANALOG SCALE;

EID: 84879504445     PISSN: 15262375     EISSN: 15264637     Source Type: Journal    
DOI: 10.1111/pme.12088     Document Type: Article

References (17)

1. Dahl JB, Rosenberg J, Dirkes WE, etal. Prevention of postoperative pain by balanced analgesia. Br J Anaesth 1990;64:518-520.
2. Buvanendran A, Kroin JS. Multimodal analgesia for controlling acute postoperative pain. Curr Opin Anaesthesiol 2009;22:588-593.
3. Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993;77:1048-1056.
4. Dray A, Bettaney J, Forster P, etal. Bradykinin-induced stimulation of afferent fibres is mediated through protein kinase C. Neurosci Lett 1988;91:301-307.
5. Rang HP, Ritchie JM. Depolarization of nonmyelinated fibers of the rat vagus nerve produced by activation of protein kinase C. J Neurosci 1988;8:2606-2617.
6. Schepelmann K, Messlinger K, Schmidt RF. The effects of phorbol ester on slowly conducting afferents of the cat's knee joint. Exp Brain Res 1993;92:391-398.
7. Cesare P, McNaughton P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci U S A 1996;93:15435-15439.
8. Burgess GM, Mullaney I, McNeill M, etal. Second messengers involved in the mechanism of action of bradykinin in sensory neurons in culture. J Neurosci 1989;9:3314-3325.
9. McGuirk SM, Dolphin AC. G-protein mediation in nociceptive signal transduction: An investigation into the excitatory action of bradykinin in a subpopulation of cultured rat sensory neurons. Neuroscience 1992;49:117-128.
10. Aley KO, Messing RO, Mochly-Rosen D, etal. Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J Neurosci 2000;20:4680-4685.
11. Minami T, Okuda-Ashitaka E, Mori H, etal. Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: Neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRepsilon subunit knockout mice. Neuroscience 2000;97:133-142.
12. Khasar SG, Lin YH, Martin A, etal. A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron 1999;24:253-260.
13. Velazquez KT, Mohammad H, Sweitzer SM. Protein kinase C in pain: Involvement of multiple isoforms. Pharmacol Res 2007;55:578-589.
14. Moodie JE, Brown CR, Bisley EJ, etal. The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Anesth Analg 2008;107:2025-2031.
15. Dina OA, Chen X, Reichling D, etal. Role of protein kinase Cepsilon and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat. Neuroscience 2001;108:507-515.
16. Dina OA, Gear RW, Messing RO, etal. Severity of alcohol-induced painful peripheral neuropathy in female rats: Role of estrogen and protein kinase (A and Cepsilon). Neuroscience 2007;145:350-356.
17. Velazquez KT, Miao FJP, Mohammad HK, etal. KAI-1678, a novel inhibitor of protein kinase C epsilon, attenuates mechanical hyperalgesia in rodent models of acute nociceptive, inflammatory and post-surgical pain. Program No. 468.16. 2008 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2008. Online 2008.