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Biology 202
2002 Second Paper
On Serendip

Lasting Effects of Pain

Peffin Lee


Once upon a typical sunny day, Mary, Susie, and Jackie are jumping rope. Unbeknownst to them, as they chant their rhymes, Mikey and Kenny hide in the bushes planning a surprise attack. Just as Mary's little feet barely lift off the ground, the two boys leap towards the girls and push them into the dirt.

"Ouch!!!" they all scream as everyone hits the dirt.

Mary is up on her feet with her knees skinned and bleeding. A smile slowly crept on her face as she tried to hold back a chuckle.

"What's so funny?" asked Mikey, as everyone turned to look at her. "Aren't you supposed to get mad and chase us around?"

Mary shrugs and looks down at her knees.

"Doesn't that hurt?" asks Jackie.

So what exactly does Mary feel when she hurts her knees?

Pain, of course. But, how exactly does she experience it?

Well, inside Mary's tissues lie nociceptors. Nociceptors are specialized sensory nerves that are activated when there is a potential for danger, such as Mary falling to the ground. The stimulation of nociceptors, first, allows large-diameter, myelinated axons to carry rapidly conducted action potentials. This causes the sensation of a sharp, well-localized, pricking or cutting pain. It is then followed by a diffuse burning or aching pain caused by more slowly propagated action potentials that are carried by smaller, less heavily myelinated axons (1).

The action potentials are generated and conveyed to the central nervous system by way of a difference in electrical potential (2). When the threshold potential difference for each nocicpetor is reached, a signal is sent to the central nervous system. As the signal continues to travel to the spinal cord, the medulla, the thalamus, and then the cerebral cortex, it must pass through a series of gates (3). According to the gate theory of pain, the awareness of pain can only get to the brain by passing through a series of gates (Melzack and Hall, 1965). To open a gate, a group of small neurons that form a "pain pool" must reach their threshold. When it is reached, the signal is allowed to be sent higher.

So as Mary and everyone else who falls to the ground, their body is undergoing this awareness of pain.

Kenny is next to stand up.

"Owww, there's sand in my leg," he whimpered unhappily.

"Hey, you pushed us, and now you're crying?," said Mary defiantly, "You are the biggest crybaby ever!"

"I am not!" shouted Kenny.

"Yea you are, I heard your mom tell my mom yesterday! She said you always cry and scream when you fall down!" said Mary.

"That's not true!" said Kenny, "my mom always said I was a premium baby!"

"Premium baby? What's that?" asks Susie.

Jackie and Mary giggle.

"What's so funny?" asks Kenny.

Mikey takes Kenny's arm. "Let's just go home Kenny."


Up until the mid-1980s, popular belief was that babies did not experience pain. Even the International Association for the Study of Pain (IASP) defined pain in two criteria: "(a) it insists on verbal expression as the only authentic source of evidence for establishing any painful experience, and (b) it suggests that the experience of pain is learned from injuries in early life" (Narsinghani). This definition excluded non linguistic beings, thus allowing physicians to perform surgery on infants without anesthesia for many years. Since then, new studies have found that pain experienced by newborns may have lasting effects.

One such groundbreaking study led by neuroscientist M.A. Ruda of the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) reported that painful stimuli delivered to rat pups shortly after birth permanently rewired the spinal cord circuits that respond to pain (4). Ruda and her colleagues began with two groups of rat pups. The first group was injected with an irritant (Freud's adjuvant) into the left hind paw when they were one day old, equivalent to that of a 24 week neonate in humans. The second group was injected at fourteen days old, equivalent to that of adolescence in humans. Both groups immediately reacted with shaking, licking of the paw, and occasional vocalization, shortly resulting in skin lesions persisting for 5 to 7 days.

About eight to twelve weeks later, the rat pups', now adults, spinal cords were stained with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) to determine the pattern of nerve fibers. The dye stained the pain-sensitive axons and indicated any appearance of new axons formed. Ruda and her colleagues discovered that the rat pups, who received the injection at one day old, had an increase of about 25% more stained axons (5) in the left side of the dorsal horn, corresponding to the side injected. The dorsal horn is the layered structure in the spinal cord that propels pain signals up to the brain. In addition, several spinal segments exhibited an increase in density of axons, specifically the caudal segments.

The increase in pain-sensitive axons can be seen in the adult rats' behavioral response to pain. Once again, the adult rats were injected with an irritant in the left hind paw, then the paw was subjected to heat. The adult rats who had been injected at one day old were much quicker to withdraw their paw than normal rats. These results coincide with the mechanisms of pain. The increased number of activated axons, result in a more intense pain. This accounts for the lower pain threshold experienced by adult rats who had been injected.

The increased sensitivity of pain was only witnessed during a distinct developmental window (5), if the injection was given at one day old to three days old, more neurons are formed. But, as the rat pup increases in age to day fourteen, the physiological and behavioral changes match that of untreated rat pups.

Therefore according to this study, abnormal stimulation during a distinct developmental window can cause changes in the pain circuits. This leads researchers to study the effects of pain on premature infants because they are still considered to be undergoing basic brain development. In my continuing revision of this paper, I will investigate how intensity of pain affects development.


1) Information on Pain

2) Information on Pain

3) Web paper Reference

4) Altered Nociceptive Neuronal Circuits After Neonatal Peripheral Inflammation

5) Neuroscience: Early Insult Rewires Pain Circuits

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