Characteristics of the nociceptive withdrawal response elicited under aware and unaware conditions
Introduction
It is common knowledge that the nociceptive withdrawal reflex (NWR) is a polysynaptic reflex under supraspinal control (Le Bars et al., 2001, Skljarevski and Ramadan, 2002). The NWR can be inhibited or facilitated depending on the context and conditions of its elicitation (see Andersen, 2007, for a comprehensive review). Among the many factors influencing the NWR, cognitive factors such as the degree of attention/awareness to the noxious stimulation may sometimes predominate. For example, performance of a mental task (Willer et al., 1979), hypnosis (Kiernan et al., 1995, Danziger et al., 1998) and relaxation (Defrin et al., 2007) during noxious stimulation induce an increase in the NWR threshold and a decrease in NWR magnitude. That is, the diversion of the subject’s attention away from the noxious stimulation may inhibit the NWR.
On the other hand, the NWR can also be facilitated. For example when subjects anticipate strong pain or receive intense noxious stimulation, the NWR threshold decreases significantly (Willer et al., 1979, Urban et al., 2004, Defrin et al., 2007). Facilitation of the NWR also occurs when a warning signal is introduced to subjects prior to evoking a stimulus (Boureau et al., 1991; Floeter et al., 1982). Thus, anticipation and preparedness for an incoming noxious stimulus induce facilitation of the NWR.
Whereas the above information relates to experimentally evoked NWR, the NWR can also be modified under natural unconstrained conditions. For example, the NWR is inhibited even when considerable pain is involved and the person is fully aware of the noxious stimulation and its consequences (e.g., when holding a boiling hot cup in order to avoid spilling its contents). On the other hand, a full-scale NWR is evoked in response to a sudden stimulus when the person is completely unaware of an incoming noxious stimulation (e.g. unintentional grounding and discharging of static electricity when touching the car in cold dry-weather). These examples suggest that the degree of a person’s awareness of the noxious stimulus and the context in which the NWR occurs may determine the nature of the supraspinal modulation over the NWR.
In this regard, it is worthwhile mentioning that the mere participation in an experiment may significantly affect the NWR. When participants are first recruited, they receive a full mandatory explanation of the experimental protocol. Consequently, even before the start of the experiment, they are subject to pre-conditioning which could interfere with the true nature of the descending control over the NWR. Creating a condition of total unawareness in order to counteract the effects of anticipation and preparedness is virtually impossible. Achieving complete unawareness by concealing from the subjects information regarding the experimental protocols is unethical. However, it is possible to minimize the subjects’ anticipation and preparedness (i.e., to reduce their awareness) to noxious stimulation by slow habituation to the experimental protocol.
In this study, we attempt to reduce awareness of the noxious stimulation by conducting many trials without stimulation until the subjects are no longer concerned with the experimental protocol. Such a “reduced awareness” condition might imitate real-life situations in which people perform tasks without being constantly conscious of potentially harmful situations.
We assume that NWR in aware and unaware conditions would obey a common motor primitive (i.e., basic motor outputs, possibly hardwired in the spinal cord). Similar motor outputs were thus expected in response to a noxious stimulus either in unaware or aware conditions. However, parameterization (tuning) of some outputs could be expected in order to accommodate (modulate) the response to the expectation of the forthcoming noxious stimulus.
Our aim was to characterize the NWR under two degrees of awareness (aware and unaware), and to explore modulatory mechanisms related to these conditions. We suggest that the facilitation of NWR under unaware conditions may manifest at two levels: (a) the muscle, seen as a decrease in the EMG onset latency before the initiation of the joint motion, and (b) the arm, the movements of which register a specific pattern corresponding to the strength of the NWR1.
Section snippets
Subjects and experimental design
Eight healthy right-handed volunteers (age 32.2 ± 8.3 years) with no health-related problems (neurological, cardiovascular or orthopedic) or perceptual impairments (visual, auditory or tactile) enrolled and completed the experiments. Informed consent was obtained from all subjects after they received a complete explanation of the protocol of the study. The human rights committee of Tel-Aviv University approved the experiments.
Subjects performed unconstrained hand movements towards visual targets
EMG onset comparisons between NWR in aware and unaware conditions
Fig. 2 presents an example of the EMG and kinematics in: (a) no-stimulation and (b) noxious stimulation conditions. In the no-stimulation condition, the EMG resembles a normal voluntary response pattern, showing multiple bursts and a longer duration than the response evoked during noxious stimulation. For movements performed without stimulation, EMG and kinematics were only weakly related to each other. In contrast, the response evoked by noxious stimulation appeared to be more clearly
Discussion
The purpose of this study was to characterize the NWR in subjects who were unaware or aware of an incoming noxious stimulation. Another aim was to explore the possible mechanisms underlying the control and modulation of the NWR under these conditions.
Common sense suggests that any change at the neuromuscular level should correspond to a parallel change at the external kinematic level. However, the relationship between EMG and kinematics has rarely been investigated within the context of
Summary and conclusions
Different awareness levels affect the muscular activity underlying the NWR (e.g., the onset latencies). In addition, different degrees of awareness affect the hand kinematics (the path and its temporal evolution). These features show that when subjects are unaware of incoming noxious stimulation the NWR is facilitated. Nevertheless, both unaware- and aware-NWR obey a similar motor response.
Future studies should include an analysis of frequency contents of the signals and a measurement of
Acknowledgements
The “Vladimir Schneider Medical Research Fund”, Tel Aviv University - Israel, granted to both authors supported the present research project. The authors wish to thank Dr. Noam Amir for his insights on methods for random signal analysis and filtering.
Ruth Defrin earned her M.Sc. and Ph.D. degrees in neurophysiology in the Department of Physiology and Pharmacology at Tel-Aviv University and is currently an assistant professor at the Department of Physical Therapy. Her main research interests are pain perception, mechanisms of central chronic pain and pain alleviation techniques.
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Ruth Defrin earned her M.Sc. and Ph.D. degrees in neurophysiology in the Department of Physiology and Pharmacology at Tel-Aviv University and is currently an assistant professor at the Department of Physical Therapy. Her main research interests are pain perception, mechanisms of central chronic pain and pain alleviation techniques.
Dario G. Liebermann earned his M.Sc. degree in motor control from the School of Kinesiology at the Simon Fraser University in Vancouver-Canada, and his Ph.D. from the Department of Applied Mathematics and Computer Sciences at the Weizmann Institute in Rehovot-Israel. His post-doc work included movement research in clinical neurosciences at the Faculty of Medicine of the University of Calgary-Canada.
He is interested in movement sciences in general, with a particular emphasis in motor control and mechanics of arm motion, posture and gait.
Today he is with the Department of Physical Therapy at the Sackler Faculty of Medicine of the Tel Aviv University, Israel, where he currently, lectures and investigates topics related to kinesiology, clinical motor control and the application of robotic technologies to improve the quality of movement of clinical populations. Currently, he is a visiting professor at the SMI center of the University of Aalborg where he investigates the supraspinal modulation of pain withdrawal responses during normal gait. He has published over 40 peer-reviewed articles and book chapters, and presented his works in over 40 international conferences.