The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation

Abstract

The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.

Keywords: hypocretin; inflammation; lateral hypothalamus; orexin; pain.

FIGURE 1

(A) LH neuronal subtypes. Simplistic diagram showing existing neuronal populations in the LH. Neuronal populations in the LH include, but are not limited to, GABA neurons, glutamate neurons, MCH-expressing neurons, galanin-expressing neurons, LepRb-expressing neurons, neurotensin-releasing neurons, substance P-releasing neurons and orexin neurons. The degree to which these neuronal populations overlap is not represented in this diagram. (B) Orexin neuron functions. Orexin neurons are involved in numerous physiological and behavioral processes including sleep/wakeful cycles, learning, memory, pain, nociception, food intake, metabolism, stress, energy balance and inflammation.