Hypothalamic deep-brain stimulation modulates thermal sensitivity and pain thresholds in cluster headache

Deep-brain stimulation (DBS) of the posterior hypothalamus has been shown to be clinically effective for drug-resistant chronic cluster headache, but the underlying mechanism is still not understood. The hypothalamus as an important centre of homeostasis is connected among others to the trigeminal system via the trigeminohypothalamic tract. We aimed to elucidate whether hypothalamic stimulation affects thermal sensation and pain perception only in the clinically affected region (the first trigeminal branch) or in other regions as well. Thus, we examined three groups: chronic cluster headache patients with unilateral DBS of the posterior hypothalamus (n = 11), chronic cluster headache patients without DBS (n = 15) and healthy controls (n = 29). Perception and pain thresholds for hot and cold stimuli were determined bilaterally in all subjects supraorbitally, at the forearm, and in the lower leg. In DBS patients, thresholds were determined with the stimulator activated and inactivated. Cold pain thresholds at the first trigeminal branch were increased on the stimulated side in the DBS group compared to healthy subjects (p = .015). The DBS group also had higher cold detection thresholds compared to non-implanted cluster headache patients (p < .05). Short-term interruption of stimulation did not induce any changes in DBS patients. Clinically relevant differences were found neither between non-stimulated cluster headache patients and healthy controls nor between the affected and the non-affected sides in the chronic cluster headache patients without DBS. These results support the notion that neurostimulation of the posterior hypothalamus is specific for cluster headache and only affects certain aspects of pain sensation.     

Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects

This study evaluated the effects of varying frequency, intensity and stimulation site, of transcutaneous electrical nerve stimulation (TENS) in an experimental model of pain. In a double-blind design 240 volunteers were randomised to one of six experimental TENS groups, a sham TENS or control (n=30 per group; gender balanced). Two TENS frequencies (110 or 4 Hz) and two intensities (strong but comfortable or highest tolerable) at a fixed pulse duration (200 micros) were applied at three sites relative to the measurement site (segmentally, extrasegmentally or a combination of these), for 30 min. Pressure pain thresholds (PPT) were measured using a pressure algometer, in the first dorsal interosseous muscle, every 10 min, during stimulation and for a further 30 min. The high frequency, high intensity segmental, and combined stimulation groups, showed rapid onset and significant hypoalgesic effects. This effect was sustained for 20 min post-stimulation in the high frequency segmental group. All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group, and none of these groups reached a clinically significant hypoalgesic level. CONCLUSIONS: The role of TENS frequency, intensity and site are pivotal to achieving optimal hypoalgesic effects, during and after stimulation. Clinical applications of these parameter combinations require further investigations.     

Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache

The nociceptive thresholds to mechanical and thermal stimuli in patients with chronic tension-type headache were compared. Palpation of pericranial tenderness was performed in 50 patients and a total tenderness score (TTS) was calculated. Palpation was repeated, and pressure pain thresholds (PPTs) were determined with a pressure algometer in the temporal and occipital regions. In 32 of the patients, pain thresholds for heat and cold and limens for detection of non-painful temperature changes were determined in the hands and the temporal regions. Twenty-four healthy volunteers served as controls. Scores obtained by manual palpation (TTS) at the first and second visit were positively correlated. A negative correlation between headache severity and PPT was found in the temporal region. A positive correlation between PPT in the temporal and occipital region was found, and PPT and TTS were negatively correlated. Thermal pain thresholds were consistently less extreme in patients compared to controls, and patients reporting severe headache on the examination day were those most sensitive to thermal pain. No difference was found between patients and controls with respect to detection of temperature changes. A correlation was found between PPT and the corresponding cold pain thresholds, but no correlation could be demonstrated between TTS and thermal pain thresholds. In conclusion, headache patients had decreased pain perception thresholds. Chronic tension-type headache might be a result of dysmodulation of nociceptive impulses, but it is likely that sensitized nociceptors also play a role.     

Alterations in electrical pain thresholds by use of acupuncture-like transcutaneous electrical nerve stimulation in pain-free subjects.

Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) was compared with a placebo treatment in altering acute electrical pain thresholds. Ten pain-free subjects underwent, on different days, an acclimatization session, an ALTENS treatment, and a placebo treatment in a cross-over design. Electrical sensation and pain thresholds were measured from the tip of the index finger bilaterally at 15-minute intervals twice before, once during, and three times after a 30-minute treatment session. The ALTENS treatment was given at 4 Hz at an intensity just below pain threshold delivered to acupuncture points in the hand and wrist. The placebo treatment was similarly delivered, except that the intensity of stimulation was just above sensation threshold. Neither the ALTENS treatment nor the placebo treatment produced a significant change in pain threshold. There was no correlation between initial pain threshold and change in pain threshold. Implications for the modulation of pain are discussed.     

Peripheral nerve stimulation for chronic pain

Electrical stimulation has been used since ancient times to treat painful conditions. Electrotherapy for pain was largely consigned to the realm of quackery until the introduction of the Gate Control Theory by Melzack and Wall in 1965 provided a rationale for direct stimulation of peripheral nerves. Since that time, peripheral nerve stimulation has been applied to the treatment of painful conditions throughout the body, beginning with the major nerves of the extremities and culminating today in precise subcutaneous field stimulation targeted to specific areas of neuropathic pain. This article reviews the history, development, and current areas of interest in peripheral nerve stimulation for the treatment of neuropathic pain.     

Trigeminal pain under vagus nerve stimulation

Three epilepsy patients treated by cyclic continuous vagus nerve stimulation (VNS) experienced trigeminal pain during the periods of stimulation, which was reported as toothache in the left lower jaw, ipsilateral to the side of stimulation. The symptom occurred with a latency of days to weeks following an increase in stimulation current intensity (SCI). Trigeminal pain was reversible with decrease in SCI, or subsided due to habituation. These findings show that clinically relevant effects of VNS on nociception may occur. Because of the late onset and variable form of this side effect, trigeminal pain may not be regarded as VNS-related which may result in unnecessary diagnostic and therapeutic procedures.     

Corneal pain evoked by thermal stimulation

The thermal sensitivity of the eyelid and cornea was compared using an automated apparatus to produce stimulus pulses of known magnitude and duration over the range 33--45 degrees C. Subjects reported only temperature sensation when the skin of the upper eyelid was tested; however, corneal stimulation in the same subjects was always perceived as nociceptive. The possibility that other ocular tissues may be involved in the pain responses was shown to be unlikely by direct experimentation or by calculation of heat flow in those tissues. Cornea and eyelid thresholds were compared in relationship to the structural and physical properties of these tissues. It was found that the nerve endings of the corneal epithelium are less sensitive to temperature change when compared to the thermal receptors of the eyelid. It is concluded that the cornea is useful for the experimental study of pain.     

Quantitative determinations of sensory and pain thresholds on human oral mucosa by argon laser stimulation.

High-energy light from an argon laser was applied to human oral mucosa in order to investigate regional pain sensitivity. Significant regional differences in sensory and pain thresholds were observed between the test sites on the hard and soft palatal mucosa, the buccal mucosa, the tongue, the lower lip, and the skin on the hand. Pain thresholds were lowest on the tip of the tongue and highest on the hard palate. Sensory and pain thresholds were influenced by different stimulus parameters: pulse duration and laser beam diameter. Blackening of the mucosa in regions with high optical reflectance, such as the hard palate, increased light absorption and, hence, reduced both thresholds significantly. Reflectance spectrophotometric measurements indicated that the hard palatal mucosa reflected argon laser light about 1.5 times more than the tip of the tongue. The different threshold values could, in part, be ascribed to different reflectance and absorption properties of the mucosal areas but also indicated substantial regional variation in pain sensitivity of the human oral mucosa. Measurement of laser thresholds is an appropriate and standardized method for investigating sensory differences in human oral mucosa and may be used to study various pain conditions, e.g., burning mouth syndrome.     

Transcutaneous electrical nerve stimulation for postlaparotomy pain

This study was designed to evaluate the transcutaneous electrical nerve stimulation (TENS) postoperative program administered by a physical therapy department. A surgeon, a physical therapist, a recovery room nurse, and unit nurses participated in the program which included preoperative evaluation and patient education, application of sterile electrodes parallel to the incision in the operating room, TENS activation in the recovery room, follow-up visits, and data collection. Seventy-five patients who underwent laparotomy and received TENS at the most comfortable machine settings were compared by chart review to 75 patients who had undergone similar surgical procedures performed by the same surgeon before TENS postoperative pain management had been instituted. The TENS was applied for an average of five days; machine settings of intensity, frequency, and pulse width tended to be midrange. The TENS group took significantly less pain medication, but the length of hospital stay was not significantly different. Patients with TENS rated their pain on 10-point scales as more intense than uncomfortable. This study demonstrated that a well-structured interdisciplinary program of postoperative TENS management can reduce the amount of pain medication taken by patients after laparotomy.     

Comparison of the effective intensity of transcutaneous electrical nerve stimulation contralateral to a pain site for analgesia

[Purpose] This study aimed to compare the effectiveness of transcutaneous electrical nerve stimulation contralateral to the pain site for analgesia to identify the effective stimulation intensity. [Participants and Methods] Ten healthy adult females were recruited for the study. The same heat stimulation was applied to the left wrist joint of each participant to induce pain, serving as the control. Transcutaneous electrical nerve stimulation was then randomly administered to the right wrist, corresponding to the same dermatome contralateral to the painful site, at the intensities of comfortable stimulation, pain threshold, and maximum pain. The effect of transcutaneous electrical nerve stimulation was assessed using a Visual Analogue Scale and by analysis of heart rate variability. [Results] The Visual Analogue Scale score was significantly lower after stimulation with the maximum pain intensity than that for control, and there were no significant differences among the intensities of comfortable stimulation, pain threshold, and maximum pain. No significant differences were found among the groups in terms of high and low-to-high frequency components. [Conclusion] Transcutaneous electrical nerve stimulation at the maximum pain intensity to the dermatome area contralateral to that of the dorsal pain site of the left wrist was considered effective.     

Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects

The effect of peripheral transcutaneous electrical nerve stimulation (TENS) on the reaction to experimental pain in human volunteers has been assessed. Placebo stimulation and electrical stimulation at moderate intensities failed to modify the response to the pain produced by conducted thermal stimuli. TENS at very high intensities did however elevate both the thermal pain threshold and the tolerance temperature. TENS at moderate intensities failed completely to alter the response to graded mechanical stimuli. The subjective pain assessment and the maximum pain tolerance produced by ischaemic pain after a submaximal effort tourniquet test were significantly modified by peripheral electrical stimulation at non-noxious intensities. The response to experimental pain can therefore be altered in man by peripheral electrical stimulation in a manner partly dependent on the sensory modality used for producing the experimental pain and on the intensity of the electrical stimulation.     

The effect of real and sham acupuncture on thermal sensation and thermal pain thresholds

OBJECTIVE: To compare the effect of real and sham acupuncture and a control intervention on thermal sensation and thermal pain thresholds. DESIGN: Single-blind, randomized controlled, repeated-measures trial. SETTING: Laboratory. PARTICIPANTS: Eighteen acupuncture-naive, healthy subjects with no history of upper-limb pathology or acupuncture contraindications. INTERVENTION: Subjects were randomly assigned (blind card allocation) to 1 of 6 possible orders of application of the interventions, which consisted of 25 minutes each of control, real, and sham acupuncture. MAIN OUTCOME MEASURES: Thermal sensation and thermal pain thresholds measured with a thermal sensory analyzer before and after each intervention. RESULTS: There were increases in cold and hot pain and cold sensation thresholds with real acupuncture. The level of increase did not differ significantly from the changes that occurred with sham acupuncture and control interventions. CONCLUSIONS: Although we observed a trend toward a decreased sensitivity to thermal pain and thermal sensation with real acupuncture, this trend did not differ significantly from the changes with control or sham interventions. Therefore, no support was provided for analgesic or placebo effects of acupuncture. The trend, combined with the relatively low power of the inferential tests applied does, however, suggest that further research is merited.     

Transcutaneous electrical nerve stimulation to relieve pain.

As a therapeutic technique, transcutaneous electrical nerve stimulation is in its infancy, but the instrumentation is rapidly becoming more sophisticated. Mindful of precautions and of the practical limitations of the technique, the practicing physician may find it worthy of serious consideration, particularly in relieving pain on a short-term basis.     

Conventional versus acupuncture-like transcutaneous electrical nerve stimulation on cold-induced pain in healthy human participants: effects during stimulation

Objectives: To compare the hypoalgesic effects of conventional transcutaneous electrical nerve stimulation (TENS) (high frequency, low intensity) and acupuncture‐like TENS (AL‐TENS, low frequency, high intensity) on cold‐induced pain. Design: Randomized controlled parallel group study comparing the effects of strong non‐painful AL‐TENS, conventional TENS and placebo (no current) TENS on cold‐pressor pain threshold (CPT) and pain intensity. Two baseline (pre‐intervention) measures and three during intervention measures of CPT and cold pain intensity (four point category scale) were recorded. Setting: Physiology laboratory in Leeds Metropolitan University. Participants: One hundred and twenty‐one healthy participants. Interventions: Each participant received one of three TENS interventions over their flexor digitorum profundus: (i) high pulse rate TENS with a strong non‐painful paraesthesia (conventional), (ii) low‐rate burst mode TENS that caused strong non‐painful phasic muscle twitching (acupuncture like) or (iii) no current (placebo) TENS. Main outcome measure: Difference between conventional TENS and AL‐TENS in cold pain threshold relative to pre‐TENS baseline after 25 min of stimulation. Results: No differences were detected for CPT or cold pain intensity during conventional TENS compared with AL‐TENS. When compared with placebo TENS, the confidence intervals for the ratio of intervention CPT to baseline CPT, for both AL‐TENS (0·966, 1·424) and conventional TENS (0·948, 1·401), were close to the positive side of one, although neither reached statistical significance. Conclusions: Unlike some previous studies, the present study detected no differences in hypoalgesia between AL‐TENS, conventional TENS and placebo (no current) TENS during stimulation.     

Influence of intense light stimulation on trigeminal and cervical pain perception thresholds

Thirty-three migraineurs and 23 healthy controls were submitted to pressure algometry before and after light-induced discomfort was elicited by progressive light stimulation in a monoblind fashion. Pressure algometries were performed on the emergence of the supraorbital, infraorbital, mental and greater occipital nerves, and over the temporal muscles, always throughout the same sequence and from right to left. Measurements were carried out before and immediately after light stimulation and after 10 min of the second algometry. The final result for each site measured at each time-point was the mean of the three measurements. Light stimulation was carried out progressively until light-induced discomfort was reported, to a maximum of 20,000 lux. A heat-blocking glass protected patients' eyes. Migraineurs presented significant and persistent drops in pain perception thresholds after light stimulation, at all sites tested (P = 0.002 to < 0.0001). These drops were not seen in controls, in whom, conversely, a less significant increase was seen on right infraorbital and left temporal muscle sites. Our results indicate that in migraineurs, light may have a relevant role in trigeminal and cervical pain perception thresholds.     

The effects of unilateral transcutaneous electrical nerve stimulation of the median nerve on bilateral somatosensory thresholds

Transcutaneous electrical nerve stimulation (TENS) is used to relieve acute and chronic pain. TENS electrodes are applied at the site of pain or in segments related to the pain, although there is limited research to support either approach. This study investigated the effects of unilateral TENS on mechanical and thermal thresholds at ipsilateral and contralateral sites in healthy human participants. Sensory perception thresholds were measured on the ipsilateral and contralateral thenar eminence of 16 volunteers for von Frey filaments, sharpness, warm, cold and heat pain. TENS was administered over the right median nerve for 10 min at 100 pulses per second (pps) and an intensity which elicited mild tingling in the hand. During TENS, ipsilateral threshold was greater than contralateral threshold for all sensory modalities, although differences were less marked for thermal stimuli. TENS effects had disappeared 30 min after TENS had been switched off although there was a tendency for thermal thresholds to remain elevated. We conclude that during stimulation, TENS elevates somatosensory thresholds within the distribution of the stimulated nerve. The rapid and short-lived ipsilateral effect is consistent with findings from animal studies and suggests a central segmental mechanism.     

Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects

Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at alpha = 0.05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n = 30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity ('to tolerance' or 'strong but comfortable') and stimulation site (segmental--over the distribution of the radial nerve or, extrasegmental--over acupuncture point 'gall bladder 34', or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 micros. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimulation period (P < 0.0005 control and sham) and was sustained for 30 min post-stimulation (P < 0.0005(control), P = 0.024(sham)). Whilst high frequency, 'strong but comfortable' intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post-stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These results may have implications for the clinical use of sensory stimulation.