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pressure response. These findings are consistent with an arterial baroreceptor inhibition mechanism for exercise-induced hypoalgesia.
and carotid sinus naturally stimulated during the systolic
reflex that facilitates withdrawal from noxious stimuli and that
has been advocated as an objective physiological correlate of
Ghione, 1996). For example, responses to noxious stimulation
are reduced by increases in blood pressure during phenylephr-
Available online at www.sciencedirect.com
Biological Psychology 78 (2such mechanisms are activation of ascending (e.g., via
stimulation of skin or muscle afferents) and descending
(e.g., via cognitive distraction) pain inhibition pathways by
stress. Specifically, stress experiences, such as exercise, may
induce hypoalgesia by increasing blood pressure which will
activate arterial baroreceptors resulting in increased supraspinal
inhibition (Ghione, 1996; Koltyn and Umeda, 2006).
Arterial baroreceptors are stretch receptors in the aortic arch
et al., 2006) but not artificial (Al’Absi et al., 2005; Edwards
et al., 2003) baroreceptor activation. Further, electrophysiolo-
gical studies have found that pain-related evoked potentials are
attenuated by natural (Edwards et al., 2007) and artificial
(Angrilli et al., 1997; Mini et al., 1995) baroreceptor
stimulation. These human findings are broadly consistent with
an extensive animal literature showing that baroreceptors are
involved in pain modulation (Randich and Maixner, 1984;1986). Thus, other mechanisms seem more likely. Examples of pain, is attenuated by natural (Edwards et al., 2001; McIntyreas exercise, the evidence from pharmacological blockade
experiments is mixed (e.g., Janal et al., 1984; Olausson et al.,Keywords: Arterial baroreceptors; Pain; Pressor response; Nociceptive flexion reflex; Exercise-induced hypoalgesia
1. Introduction
Human studies have established that dynamic exercise is
associated with a reduction in electrical, thermal, and
mechanical pain (Koltyn, 2000), however, the mechanism for
this phenomenon has not been established. Although endo-
genous opioids have been suggested as mediators of
hypoalgesia (i.e., reduction in pain) induced by stress such
upstroke of the pulse pressure wave and sensitive to both
absolute pressure and rise in pressure (Eckberg and Sleight,
1992). Pain can be reduced during activation of baroreceptors
by vasoactive drugs that increase blood pressure (Larbig et al.,
1985; Rockstroh et al., 1988), maneuvers that increase blood
pressure (Agarwal et al., 2005), and suction of the neck region
that stretches the receptors (Rau and Elbert, 2001). Evidence
suggests that the nociceptive flexion reflex (NFR), a spinal# 2008 Elsevier B.V. All rights reserved.Effects of isometric exercise on p
Christopher Ring *, Louisa
International Centre for Health & Exercise Research
Received 26 October 200
Available onlin
Abstract
Sensitivity to pain is reduced during exercise. The underlying mecha
mechanism may contribute to this exercise-induced hypoalgesia phen
blood pressure during graded isometric exercise, which activate barorec
exercise on pain in 24 normotensive young men. Electrocutaneous stimu
handgrip exercise at 1%, 15%, and 25% of their maximum voluntary co
following the delivery of each stimulus. Nociceptive flexion reflex (N
physiological correlates of pain. Pain ratings were attenuated by graded
responses and thresholds were unchanged by exercise. Blood pressure in
using analyses of covariance indicated that the reduction in pain with* Corresponding author. Tel.: +44 121 414 4115; fax: +44 121 414 4121.
E-mail address: c.m.ring@bham.ac.uk (C. Ring).
0301-0511/$ – see front matter # 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.biopsycho.2008.01.008n are mediated by blood pressure
dwards, Maria Kavussanu
niversity of Birmingham, Birmingham B15 2TT, UK
ccepted 21 January 2008
February 2008
has yet to be established. One possibility is that a baroreceptor-related
enon. Accordingly, this study examined whether increases in arterial
ors in the aortic arch and carotid sinus, could account for any effects of
ere delivered to the sural nerve while participants performed isometric
ction (MVC). Participants provided a pain intensity rating immediately
) responses and thresholds were also determined to provide objective
metric exercise in a linear fashion, whereas nociceptive flexion reflex
ased in proportion to the force of the contraction. Mediational analyses
ercise was substantially accounted for by the magnitude of the blood
www.elsevier.com/locate/biopsycho
008) 123–128ine infusion only in animals with intact baroreceptors (Dworkin
et al., 1979). In sum, evidence has accumulated to support a
baroreceptor-related pain modulation mechanism.

sycSeveral studies have found that isometric exercise, which
increases blood pressure in proportion to the percentage of the
maximum voluntary contraction (MVC) (Lind, 1984), reduces
mechanical (Koltyn et al., 2001; Kosek and Ekholm, 1995;
Kosek et al., 1996; Kosek and Lundberg, 2003; Staud et al.,
2005) and thermal (Staud et al., 2005) pain. The current study
examined electrocutaneous pain when participants contracted
hand flexor muscles at 1%, 15%, and 25% of their MVC.
Contractions at the higher intensities were expected to
stimulate arterial baroreceptors by increasing blood pressure
by approximately 10 and 25 mmHg, respectively (Boushel
et al., 1998; Williamson et al., 1996). Preliminary evidence
suggests that the NFR, an objective physiological correlate of
pain (Sandrini et al., 2005), is attenuated by dynamic exercise
(Guieu et al., 1992). Accordingly, the present study also
examined the NFR during isometric exercise.
The aims of the present study were twofold. First, to assess
the effects of graded isometric exercise upon pain ratings and
the NFR, a physiological correlate of pain. Second, to
determine the extent to which any exercise-induced hypoalge-
sia was mediated by increases in arterial pressure. As such, the
study makes important contributions to the literature by being
the first to examine the effects of isometric exercise on
electrocutaneous pain and the NFR, and, importantly, the first to
determine the contribution of a baroreceptor-related mechan-
ism to reduced pain sensitivity during exercise.
2. Method
2.1. Participants
Twenty-four healthy adult Caucasian right-hand dominant men with a mean
age of 21 years (S.D. = 3), mean weight of 74 kg (S.D. = 7), and mean height of
180 cm (S.D. = 6) participated in the study. Their mean (S.D.) resting systolic
and diastolic blood pressures were 121 (9) and 63 (6) mmHg, respectively; all
participants were normotensive. Participants were asked to refrain from
analgesic medication for 3 days and from strenuous physical activity for
12 h prior to testing. The local research ethics committee approved the study
protocol, and volunteers gave informed consent to participate.
2.2. Physiological measurements
Participants sat upright in a comfortable chair with their left ankle supported
so the knee was flexed at 358. A computer and Micro1401 (CED) were
programmed in Spike2 to present stimuli and record responses. Blood pressure
was measured using an oscillometric sphygmomanometer (Dinamap, Critikon)
and a brachial cuff attached to the participant’s upper left arm. Electromyo-
graphic activity of the left biceps femoris musclewas recorded at 2000 Hz using
a Bagnoli-2 amplifier (20–450 Hz, 10,000) and single differential surface
electrode (Delsys) with a separate reference electrode (for further details see
Edwards et al., 2001). The sural nerve was stimulated using a constant current
stimulator with 400 V compliance (DS7A, Digitimer) and bar electrode (Nico-
let) that was secured posterior to the ankle. Sites were prepared using alcohol
swabs and abrasive gel until electrode impedance was <10,000 V. Conductive
cream was applied to electrode contacts.
2.3. Pain
Pain was assessed concurrently using a 0–100 numerical rating scale, with
anchors of 0 (no pain) and 100 (maximum tolerable pain). Aversion of the scale
was located on the wall in front of participants. After each sural nerve
C. Ring et al. / Biological P124stimulation had been delivered, participants were asked to rate the intensityof the sensation associated with each electrocutaneous stimulus by calling out a
number between 0 and 100. Previous research in our laboratory indicates that
the pain sensation associated with sural nerve stimulation is typically described
by participants as sharp, shooting and stabbing.
2.4. Nociceptive flexion reflex
Electrical stimulation of the sural nerve of sufficient intensity to stimulate
small diameter A-delta nociceptive fibers is used to elicit a withdrawal response
from the ipsilateral biceps femoris muscle (Willer, 1983). This polysynaptic
spinal reflex subserves withdrawal from noxious stimuli to avoid tissue injury,
and accordingly, there is a close correspondence between the thresholds for
nociceptive withdrawal and pain perception (Hugon, 1973; Willer, 1977). The
NFR threshold was determined using a 4-2-1 adaptive up–down staircase
procedure. The sural nerve was stimulated by five 1 ms square-wave pulses
at 250 Hz, 200 ms into each 1 s trial. The NFR response was operationally
defined as a mean rectified electromyographic response in the 90–150 ms post-
stimulus interval that exceeded mean rectified electromyographic activity
during a 60 ms pre-stimulus baseline interval (65 to 5 ms) by at least
1.5S.D. Stimulus intensity increased in 4 mA steps, starting at 0 mA, until the
NFR was first detected, and then decreased in 2 mA steps until the NFR was no
longer detected. The staircase continued in 1 mA steps for four more reversals,
which were averaged to yield the NFR threshold (mA). A variable (15, 20, and
25 s) inter-trial interval was used.
2.5. Procedure
Participants completed a single testing session. First, they performed three
maximal contractions using a handgrip dynamometer (Lafayette) while resting
their right arm on a support at a constant angle (Kahn et al., 1986). The peak
forces were recorded and the MVC was determined as the largest (M = 48.5,
S.D. = 7.7 N) of the three contractions (Kilbom et al., 1983). After instrumenta-
tion and instruction (30 min), they sat quietly and rested for 5 min while their
blood pressure was measured three times; these measures were obtained during
1, 3, and 5 min.
Participants were then familiarized with the NFR procedure by having their
sural nerve stimulated at various intensities. Next, their NFR threshold was
determined under three isometric exercise conditions expected to produce
graded increases in blood pressure: 1% MVC, 15% MVC, and 25% MVC
(see Goldberg et al., 1982). In each condition, the participant was required to
squeeze the dynamometer continuously. The required force was indicated to
participants by placing a bright green strip on the dynamometer’s analog force
output scale; participants were asked to squeeze the dynamometer so that the
black analog pointer, whose position indicated the current force output, was
aligned with the green strip. The 1% MVC condition served as a control
condition. Based on previous research showing that 25% MVC is associated
with a time to fatigue of approximately 6 min (Kilbom et al., 1983), the intensity
of the 25% MVC condition was chosen to allow sufficient time for an NFR
threshold to be determined.
Each condition lasted as long as required to obtain an NFR threshold; the
mean number of trials needed for this was 13 (S.D. = 3) trials and the mean
duration of each NFR determination was 4.5 (S.D. = 1) min. Conditions were
counterbalanced across participants to prevent order effects (Goldberg et al.,
1982); analyses confirmed that there were no significant order effects for pain or
the NFR. Participants were instructed to breathe normally while exercising to
prevent the Valsalva maneuver (Mancia and Mark, 1983) that can also increase
blood pressure. Blood pressure measurements were initiated 30, 90, 150, and
210 s into each condition, which was followed by a 5 min rest to allow blood
pressure to return to baseline levels (Boushel et al., 1998; Fontana et al., 1993).
Finally, participants rested for 5 min while their blood pressure was again
measured three times; the measurements were obtained in 1, 3, and 5 min.
2.6. Data reduction and analysis
The pain ratings associated with each of the electrocutaneous stimulations
(M = 13, S.D. = 3 ratings) were averaged to produce an overall pain intensity
rating for each exercise condition. In addition, the ratings associated with the
hology 78 (2008) 123–128three peak stimulus intensities (i.e., the reversal points in each staircase) were