The main focus of our group is on Opioids and State-Dependent Control of Pain.
The brain has specific systems for processing stimuli that have emotional and motivational significance, and triggering appropriate changes in behavioural state. This can have a profound influence on pain and the effects of pain-relieving drugs. Higher brain centres such as the amygdala and nucleus accumbens can initiate state-dependent effects on pain-inhibiting or pain-facilitating pathways that exert control over the lower brain stem and spinal cord. We are especially interested in how these mechanisms are affected by opioids—the large family of drugs and natural endogenous neurotransmitters, functionally related to morphine.
Repeated or long-term use of opioids leads to drug induced changes in mood, emotional, and motivational states that can have profound effects on the sensation of pain and how it is controlled by analgesic drugs. We are using rats for brain activitation mapping studies that are identifying specific brain pathways that are affected by different patterns of opioid treatment. We are also one of the PMRI groups participating in the Spinal Cord Injuries Program funded by the NSW Ministry of Science and Medical Research. In this case we will be studying how the transmission of non-noxious and painful sensory information from spinal cord to brain, is disrupted and altered by spinal cord injury.
The clinical use of analgesic opioid drugs for pain relief continues to be confounded by tolerance. This loss of effect develops over time when drugs are used continuously or repeatedly. This means higher doses or stronger drugs must be used to achieve the same level of pain relief, which increases side effects and risk to the patient. Tolerance, measured by a loss of opioid signaling, can be induced even in single isolated cells. We are currently researching these processes using cell-lines that have been engineered to express the mu-opioid receptor. We also have project funding from Northern Sydney Health and ANZCA to extend these studies to peripheral sensory nerve cells isolated from rats and mice. We will be using these systems to study how inflammation affects opioid signaling and tolerance in these pain-sensing cells.
Marchant NJ, Densmore VS, Osborne PB (2007) Coexpression of prodynorphin and corticotrophin-releasing hormone in the rat central amygdala: evidence of two distinct endogenous opioid systems in the lateral division. J Comp Neurol, 504(6), 702-15.
Kalous A, Osborne PB, Keast JR (2007) Acute and chronic changes in dorsal horn innervation by primary afferents and descending supraspinal pathways after spinal cord injury. J Comp Neurol, 504(3), 238-53.
Hamlin AS, McNally GP, Osborne PB (2007) Induction of c-Fos and zif268 in the nociceptive amygdala parallel abstinence hyperalgesia in rats briefly exposed to morphine. Neuropharmacology, 53(2), 330-43.
Christie MJ, Osborne PB (2007) Opioid Electrophysiology in PAG. In: Willis WDJ, Schmidt, Robert F., editor. Encyclopedia of Pain. Heidelberg: Springer, Heidelberg, pp 1532-1534.
Chieng BCH, Christie MJ, Osborne PB (2006) Characterization of neurons in the rat central nucleus of the amygdala: Cellular physiology, morphology, and opioid sensitivity. The Journal of Comparative Neurology, 497(6), 910-927.
Osborne PB, Halliday GM, Cooper HM, Keast JR (2005) Localization of immunoreactivity for deleted in colorectal cancer (DCC), the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents. Neuroscience, 131(3), 671-81.
Buller KM, Hamlin AS, Osborne, PB (2005) Dissection of peripheral and central endogenous opioid modulation of systemic interleukin-1beta responses using c-fos expression in the rat brain. Neuropharmacology, 49(2), 230-242.
Hamlin AS, Buller KM, Day TA, Osborne PB (2004) Effect of naloxone-precipitated morphine withdrawal on c-fos expression in rat corticotropin-releasing hormone neurons in the paraventricular hypothalamus and extended amygdala. Neuroscience Letters, 362(1), 39-43.
Connor M, Osborne PB, Christie MJ (2004) Mu-opioid receptor desensitization: Is morphine different? Br J Pharmacol, 143(6), 685-696.
Bengtson CP, Lee DJ, Osborne PB (2004) Opposing electrophysiological actions of 5-HT on noncholinergic and cholinergic neurons in the rat ventral pallidum in vitro. J Neurophysiol, 92(1), 433-43.
Kanjhan R, Osborne PB, Ouyang M, Keast JR (2003) Postnatal maturational changes in rat pelvic autonomic ganglion cells: a mixture of steroid-dependent and -independent effects. J Neurophysiol, 89, 315-23.
Borgland SL, Connor M, Osborne PB, Furness JB, Christie MJ (2003) Opioid agonists have different efficacy profiles for G protein activation, rapid desensitization, and endocytosis of mu-opioid receptors. J Biol Chem, 278(21), 18776-84.
Osborne PB, Vidovic M, Chieng B, Hill CE, Christie MJ (2002)Expression of mRNA and functional alpha(1)-adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons. Br J Pharmacol, 135(1), 226-32.
Hamlin A, Buller KM, Day TA, Osborne PB (2001) Peripheral withdrawal recruits distinct central nuclei in morphine-dependent rats. Neuropharmacology, 41(5), 574-81.
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