Norepinephrine & Pain

Norepinephrine's effects on pain depend on whether it (1) is acting as a neurotransmitter in the central nervous system affecting the spinal cord and brain, or (2) is functioning as a hormone released into the bloodstream to affect tissues throughout the body.

Types of Pain

• Norepinephrine affects acute and neuropathic pain. In acute, or nocioceptive, pain, peripheral nerves at damaged tissue sites relay signals to the brain through the spinal cord to alert the brain and body to respond to and limit damage. Neuropathic pain is chronic and is caused by damage to the peripheral and central nervous systems due to persistent, localized acute pain.

Effects on Acute Pain

• The hormone norepinephrine is released by the adrenal gland. When norepinephrine is released into the bloodstream, it excites the sympathetic nervous system and generally increases pain.

Acute Pain Mechanisms

• Norepinephrine increases muscular tension, which releases lactic acid that produces tissue pain. Further, norepinephrine reduces oxygen flow to tissues, causing pain by slowing the removal of lactic acid. These mechanisms may be implicated in some of the pain associated with fibromyalgia, chronic fatigue syndrome, osteoarthritis, and other muscular/skeletal diseases.

Effect on Neuropathic Pain

• When norepinephrine functions as a neurotransmitter within the brain and spinal cord, it generally reduces neuropathic pain.

Neuropathic Pain Reduction Mechanisms

• Norepinephrine reduces neuropathic pain by stimulating specific areas of the dorsal (rear) horn of the spinal cord. Norepinephrine also reduces neuropathic pain by affecting the amygdala, hypothalamus and other emotional modulation areas of the brain. Some of the relief is direct analgesic (i.e., pain relief), and some relief is moderated by the effect that norepinephrine has on mood, depression and reduced sympathetic nervous system activity.

Medications

• Tricylic antidepressants such as imipramine, amitriptyline, and doxepine increase the availability of norepinephrine in the central nervous system and thereby reduce neuropathic pain.