Patients who experience acute, transient or persistent pain often repor6t complete or partial loss of appetite. Despite its high prevalence, the neural basis of pain-induced anorexic behavior is unknown. The premise for this proposal is the association between pain and anorexia, which is particularly striking during attacks of migraine headache. The objectives of the current proposal are to gain novel understanding of the neurobiology of anorexia induced by pain using our animal model.
The specific aims i n this proposal have been born out of our ongoing basic and clinical studies on the pathophysiology of migraine and how intracranial pain signals research the hypothalamus.
Specific Aim 1 will determine whether stimulus of the dura, which we use as a model for intracranial pain (such as migraine), can activate neurons in brain areas that mediate anorexia.
Specific Aim 2 will identify the neural pathways that transmit intracranial pain signals to hypothalamic neurons that regulate feeding behavior.
Specific Aim 3 will identify the chemical phenotype of the neurons activated by dural stimulation and determine whether they express molecules (such as CCK and leptin) that were shown recently to suppress appetite and used clinically to fight obesity.
Specific Aim 4 a will determine whether dural stimulation can suppress feeding behavior in our animal model and whether it resembles the suppression of feeding behavior during migraine attack in human subjects.
Specific aim 4 b will test our working hypothesis that the suppression of feeding behavior by intracranial pain is mediated by activation of parabrachial neurons that contain CCK and ventromedial hypothalamic neurons that exhibit receptors to anorexic neuropeptide CCK and/or the hormone leptin. This grant proposal offers a unique collaborative effort of expertise from the field of feeding behavior and the field of pain and migraine. This interdisciplinary approach provides an opportunity to use state-of-the-art techniques to examine neuroanatomical, neurophysiological, molecular, and behavioral aspects of the neural mechanism that enables pain to induce anorexia; a biological phenomenon of distinct clinical relevance that affects millions of pain patients in the US.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (01))
Program Officer
Kusiak, John W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
Levy, Dan; Burstein, Rami; Kainz, Vanessa et al. (2007) Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130:166-76
Zhang, Xi-Chun; Strassman, Andrew M; Burstein, Rami et al. (2007) Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther 322:806-12
Jakubowski, Moshe; Silberstein, Stephen; Ashkenazi, Avi et al. (2005) Can allodynic migraine patients be identified interictally using a questionnaire? Neurology 65:1419-22
Burstein, Rami; Jakubowski, Moshe (2005) Unitary hypothesis for multiple triggers of the pain and strain of migraine. J Comp Neurol 493:9-14
Jakubowski, Moshe; Levy, Dan; Goor-Aryeh, Itay et al. (2005) Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache 45:850-61
Burstein, Rami; Jakubowski, Moshe; Levy, Dan (2005) Anti-migraine action of triptans is preceded by transient aggravation of headache caused by activation of meningeal nociceptors. Pain 115:21-8
Burstein, Rami; Jakubowski, Moshe (2005) Implications of multimechanism therapy: when to treat? Neurology 64:S16-20
Burstein, Rami; Jakubowski, Moshe (2004) Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol 55:27-36
Burstein, Rami; Collins, Beth; Jakubowski, Moshe (2004) Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 55:19-26
Levy, Dan; Jakubowski, Moshe; Burstein, Rami (2004) Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc Natl Acad Sci U S A 101:4274-9

Showing the most recent 10 out of 11 publications