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What is Pain?

For many, pain is an indescribably awful feeling that causes suffering and emotional distress.  It is a sensation that is so unpleasant – so unbearable – that most people will go to great lengths to avoid it.  For others, enduring pain has become a rite of passage (tattoo, anyone?) that signifies mental strength and discipline.  The ceremony, however, does not diminish the pain itself or one’s primal urge to avoid it.  Regardless, many people live a relatively pain-free life, and those that choose to endure pain do so on their own free will.  For those that suffer from neuropathic pain, however, pain has become an unavoidable specter that haunts every moment of their lives.

Neuropathic pain is a chronic pain syndrome that is often the result of tissue or nerve damage.  A commonly known form of neuropathic pain is “phantom limb syndrome,” in which an amputee continues to feel pain in his or her nonexistent limb.  Although there are many ways that a person can develop neuropathic pain, the common cause is that those nerve fibers become “overactive” and send continuous pain signals to the brain, even in the absence of any noxious stimuli!  For many, this constant and severe pain is often felt as a sensation of “pins and needles” or burning pain.

One form of neuropathic pain, termed peripheral neuropathic pain, is thought to be a result of overactive neurons in a region of the spinal cord called the dorsal root ganglia.  These neurons directly sense pain and other tactile stimuli in the body and communicate that information to the spinal cord.  From there, the information travels up to multiple regions of the brain where the “pain” sensation is perceived.  Although pain may cause a plethora of sensations and emotions, such as distress, anxiety, depression, anger, etc., the most basic form of pain is simply the communication of a “pain signal” by neurons in the dorsal root ganglion to the spinal cord.  Since the most common form of neuronal communication is via action potentials, one may view the duration and intensity of pain as simply the generation of action potentials by a handful of neurons.  In neuropathic pain syndromes, it is thought that these neurons become overactive and simply produce too many action potentials, which are then transferred to the brain and perceived as pain.

Spinal Cord Pain Knowing Neurons Dorsal Root Ganglia Neuropathic Pain Sensation Information C-fiber

A recent article published in the Journal of Nature Neuroscience identified a protein that may play a key role in regulating just how active dorsal root ganglion neurons are.  Specifically, subsets of neurons called C-fibers (carriers of “burning” pain) were shown to express a previously-uncharacterized protein called TMEM16C.  This study discovered that the TMEM16C protein pairs up with an ion channel called “Slack” and regulates the activity of C-fiber neurons.  Slack is an interesting ion channel that senses the sodium ions that flux into the neuron during the upstroke of an action potential and opens a potassium channel that helps repolarize the neuron’s membrane potential.  In non-scientist lingo, this makes the action potential shorter and stops the communication to other neurons.

When the scientists recorded action potentials in neurons that lacked TMEM16C, they found that the action potentials lasted longer than normal.  If the duration of an action potential is related to the intensity of pain sensations, then broader action potentials are likely to transmit a larger “pain signal” to the brain.  The researchers then made a genetically modified mouse that lacked TMEM16C and found that these mice were much more sensitive to heat pain than normal mice!  These findings are quite promising because other studies have shown that chronic pain leads to lower TMEM16C levels, potentially causing hyperactive neurons.

Dorsal Root Ganglion Neuron Knowing Neurons Ryan Jones Action Potential TMEM16C

Although there is much more research to be done on TMEM16C’s role in pain and pain disorders, the findings in this study are promising because they have identified a new protein that regulates the activity of neurons responsible for some forms of pain.  Future pharmaceutical drugs may be developed that modulate TMEM16C and (hopefully) the pain itself!


Written by Ryan Jones.



Gadotti V.M. & Zamponi G.W. (2013). TMEM16C cuts pain no SLACK, Nature Neuroscience, 16 (9) 1165-1166. DOI: 10.1038/nn.3497

Huang F, Wang X, Ostertag E.M., Nuwal T, Huang B, Jan Y, Basbaum AI, & Jan L.Y. (2013). TMEM16C facilitates Na+-activated K+ currents in rat sensory neurons and regulates pain processing, Nature Neuroscience, 16 (9) 1284-1290. DOI: 10.1038/nn.3468

Images made by Ryan Jones and adapted from Wikimedia Commons


One thought on “What is Pain?

  • Reblogged this on EngageKids and commented:
    As a member of a family with varying pain responses on the extreme ends (both over and underesponsiveness) I found this interesting

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