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Pain Part II: Why Treat Pain? and How Pain Travels in the Body

January 31, 2014

Pain is a normal response by the body to various insults, and mild transitory pain can be protective for injured tissues. However, as pain increases in intensity and/or becomes a chronic problem, it becomes counterproductive and can have several debilitating health effects. Un- or under-managed pain in human and veterinary medicine has been associated with:

  • Delayed healing (wounds, post-surgical)
  • Increased mortality (death) rate after procedures and illnesses
  • Depressed immune function
  • Increased blood pressure
  • Impaired cognition (memory, attention, reaction time)
  • Irritability and other behavioral changes
  • Changed nerve function that lowers an individual’s future pain threshold
  • Physiologic changes that cause further damage to painful tissues

Some of these complications occur because of the complex nature of the pain pathways in the body and their “plasticity” or changeability in response to ongoing stimulation. Others occur due to the effects of physiologic stress that prolonged pain has on the body. In order to fully appreciate the importance of pain management and how pain may be managed, it is helpful to have some basic understanding of how we feel the sensation of pain in the body.

Pain is transmitted from the site of pain to the brain through multiple levels of nerve cells (neurons) that communicate with each other using electrical impulses and chemicals. As part of this network, there are also neurons that carry messages from the brain to inhibit (lessen) our perception of pain.

The first step is stimulation of a type of cell called a first order neuron or nociceptor. These are nerve cells with specialized endings that detect stimuli such as cold, heat, crush, cell damage, or other painful processes; in response to these stimuli nociceptors do two things: 1. Release chemicals called inflammatory mediators that activate their neighboring nociceptors 2. Transmit an impulse to the next nerve in the pain pathway, which is found in the spinal cord. The more nociceptors are activated, the more impulses will be sent to the spinal cord.

The second step is stimulation of the second order neurons in the spinal cord. For simplicity’s sake it is easiest to think of these as a single type of cell, but in reality the types and arrangement of second order neurons in the spinal cord is quite complex. These second order neurons receive signals from the first order neurons and send their own signals to their neighboring second order neurons and to the brain. They may also receive inhibitory signals from the brain that are passed back down to the first order neurons to help block perception of pain.

Our conscious perception of pain occurs in the brain, by cells called third order neurons. Again, for simplicity’s sake it is easiest to think of them as one unit but in reality the signals from second order neurons are processed successively through more than one area of the brain, where they may be worsened or lessened by other factors such as strong emotions, stress, fatigue, or anxiety.

If pain is prolonged, it results in the constant presence of signals at all stages of the pain pathway and can lead to a state called hypersensitization where all of the neurons are more “irritable” and more likely to be activated to send their signals on to the next stage. At the site of pain, large amounts of the inflammatory mediators collect and hypersensitize the first order neurons; this is called peripheral hypersensitization. This in turn leads to a constant barrage of signals sent to the second order neurons in the spinal cord, called central hypersensitization. Central hypersensitization can then lead to further problems: 1. Allodynia, the perception of non-painful stimulus as painful (for example, being touched at a location separate from the original source of pain) 2. Hyperalgesia, a painful stimulus is perceived as more painful than it “should” be, and/or 3.Neuropathic pain, a state where the second order neurons are so overstimulated that they begin to initiate impulses themselves without any input from the first order neurons. Once neuropathic pain develops, the sensation of pain may still be felt even if the original source of pain heals, is no longer painful, or is no longer present (for example, phantom pain of an amputated limb).

It is not necessary to have a degree in neurology to understand pain.The take-home messages today are: 1. The potential for the development of chronic and debilitating abnormal pain states and their effects on overall health makes it is very important to treat pain 2. The way pain is transmitted through the body gives us the opportunity to combine multiple techniques and drugs that target the multiple steps in the pain pathway in order to manage it more effectively than using any single technique or drug alone.

Next time, we will start to explore what options are available for targeting these various steps and how to combine them.


Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. New England Journal of Medicine. 1992 Jan 2;326(1):1-9

Doubell TP et al. The dorsal horn: state-dependent sensory processing, plasticity, and the generation of pain. In: Wall, PD, Melzak R, eds. Textbook of Pain 4th ed. New York: Churchill-Livingston, 1999, 165-182

IASP Pain Clinical Updates, Carr DB ed. July 2007, XV:4

Giordano J, The Neuroscience of Pain and Analgesia, In: Weiner’s Pain Management, Boswell, Cole ed’s, 7th ed. Taylor & Francis, Boca Raton FL 2006

Hermann C, et al. Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain 2006 124:278-285

Honore P, Menning PM, Rogers SD, et al. Neurochemical plasticity in persistent inflammatory pain. Prog Brain Res. 200;129:357-363

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