The hypothalamus is believed to play important roles in several aspects of nociception. Previously, nociceptive information was thought to reach hypothalamic neurons through indirect, multisynaptic pathways. However, we have found that thousands of neurons throughout the length of the spinal cord in rats send axons directly into the hypothalamus, and many of these axons carry nociceptive information. The axons often follow a complex course, ascending through the contralateral spinal cord, brainstem, thalamus and hypothalamus. They then cross the midline and enter the ipsilateral hypothalamus, turn posteriorly, and continue into the ipsilateral thalamus. These axons might provide nociceptive information to a variety of nuclei in the thalamus and hypothalamus bilaterally.