sensation (“first pain”). This is followed by a diffuse burning sensation approxi-
mately 1 s later (“second pain”) (Price et al. 1977 ). The activation of the motor
withdrawal of the hand is a protective reflex to minimize potential tissue damage
from the insult and is not related to the conscious sensation. The sharp, pricking
“first”pain is related to information encoded by the small, myelinated Aδperipheral
nerves that provide information about temperature and touch as well as pain. These
nerves conduct impulses at >1 m/s. The diffuse, burning“second”pain is related to
information encoded by unmyelinated C peripheral nerves that provides informa-
tion about higher intensity temperature and pressure as well as pain. These nerves
transmit information at a slower rate, approximately 0.7 m/s. The 1-s delay in
“first”and“second”pain is related to the different amount of time it takes for the
information to travel from thefinger to the brain by these two nervefiber types.
There are other features of“first”and“second”pain that help us understand
factors associated with the onset and maintenance of persistent clinical pain. If a
healthy, pain-free subject rates the pain intensity of“second pain”in a series of heat
pulses (temperatures≥45 °C) of varying frequencies of stimulation to the hand or
foot, the pain experience changes with changes in frequency. If the heat pulses are
presented at 5 s intervals, the rated“second”pain intensity using VAS ratings is
unchanged and will be the same for thefirst and fourth stimulus. If the frequency of
stimulation increases to once every 2.5 s, the rated“second”pain intensity will
increase with each of the four stimuli.“First”pain does not increase with changes in
frequency. We call this enhanced increase summation of“second”pain with the
succession of pulses“windup”(Price et al. 1977 , 1994 ).
This phenomenon of“windup”occurs if we increase the number of pulses as
well. So, when a subject rates the pain intensity for each stimulus in a series of ten
pulses delivered at a frequency of one every 2 s, the judged pain intensity also
increases with each pulse. Subjects will also report that after the tenth pulse, there is
a lingering pain aftersensation at 15 s after stimulation is terminated that is gone by
120 s (Price et al. 1977 , 1994 ). The increased sensitivity to each successive stim-
ulus is referred to as hyperesthesia which is a common feature of persistent clinical
pain. However, in persistent pain patients, the magnitudes of these effects are
enhanced (Price et al. 1992 , 2002 ; Staud et al. 2001 ,2003a). Furthermore, in
clinical persistent pain (e.g.,fibromyalgia, irritable bowel syndrome, postherpetic
neuralgia or “shingles pain”, tempromandibular disorders), the enhanced pain
experience (lower pain threshold) is oftentimes associated with non-noxious stim-
ulation (allodynia) (Woolf 2011 ). For example, patients suffering from postherpetic
neuralgia afflicting the trunk will complain that the movement of their shirt or
blouse across the skin (light touch) is painful.
Pain patient ratings of“windup”and the lingering aftersensations have provided
insights into nervous system changes in these conditions. For example,
fibromyalgia patients and control subjects rated the pain intensities of each of ten
pressure pulses (1 kg/s and maintained for 2.5 s) delivered every 2 s and every 5 s
and their aftersensations at 15 and 120 s (Staud et al. 2007 ). Both patients and
controls rated the pain intensities of pulses delivered every 2 s as greater than those
delivered every 5 s. This indicated that“windup”was similar in both groups.
110 M.W. Heft and M.E. Robinson