Differential Nerve Block Research Articles

The Diagnostic Dilemma of a Genitofemoral-ilioinguinal Overlap Syndrome

Background: It is sometimes difficult to clinically delineate genitofemoral and ilioinguinal neuralgias because of the overlap in the clinical symptomatology. Case description: A young male with a past history of transurethral removal of ureteral calculi presented with severe, debilitating neuropathic pain in the groin. He had hyperpathia and allodynia in the distribution of genitofemoral nerve, and hence a clinical diagnosis of genitofemoral neuralgia was made. An ultrasound guided diagnostic block of the genitofemoral nerve with local anesthetic produced only a mild reduction in pain (VAS 2 reduction). A repeat diagnostic block of the ilioinguinal nerve produced complete resolution of pain. Literature search showed a limited number of case reports of ultrasound guided blocks for genitofemoral neuralgia; and overlap syndromes have been addressed with differential nerve blocks. Clinical relevance: Our hypothesis is that an aberrant reinnervation from the ilioinguinal to genitofemoral nerve may present with features favoring a genitofemoral neuralgia. In situations where radiofrequency treatment is being considered, such cases may pose a failed intervention if both nerves are not separately targeted.

Genitofemoral neuralgia: a review.

Genitofemoral neuralgia is a cause of neuropathic pain that is often debilitating in nature. It is characterized by chronic neuropathic groin pain that is localized along the distribution of the genitofemoral nerve. The symptoms include groin pain, paresthesias, and burning sensation spreading from the lower abdomen to the medial aspect of the thigh. It may present with scrotal pain in male, while females experience symptoms radiating to the labia majora and mons pubis. Genitofemoral neuropathy has been attributed to iatrogenic nerve injury occurring during inguinal and femoral herniorrhaphy, with cases developing after both open and laparoscopic techniques. Diagnosis of genitofemoral neuralgia can be challenging, due to the overlap in sensory distribution the nerve shares with the ilioinguinal and iliohypogastric nerve. Differential nerve blocks are recommended in effort to differentiate the nerves when patients present with lower abdominal and groin pain. Once a diagnosis has been made, there exist several treatment options for genitofemoral neuralgia ranging from medical management, non-invasive injections, and surgery. Literature has also brought light to radiofrequency ablation and cryoablation performed under ultrasound guidance as emerging treatments. The aim of the current article is to review the anatomy, diagnostic techniques, and treatment options for patients with genitofemoral neuralgia.

Differential axillary nerve block for hand or forearm soft-tissue surgery

This study determined the effective concentration of ropivacaine required to produce the type of differential block known as sensory block with mobilization, for adequate analgesia after forearm or hand soft tissue surgery by axillary brachial plexus block. Forty-four patients were enrolled, and ultrasound-guided axillary nerve block with nerve stimulation was achieved using 16 mL of ropivacaine in total. Postoperative analgesia and sensory/motor function, side effects, the use of rescue analgesics, and the patient satisfaction score were evaluated 24 h after surgery. The effective concentration of nerve block was calculated by probit analysis. Eighteen patients achieved differential block and were sufficiently satisfied with the block, which was significantly better than the patient satisfaction obtained with incomplete differential block. The maximum effective concentration of 6 mL of ropivacaine needed for differential block was calculated as 0.1285 %, which meant that 71 % of the patients experienced both sensory block and maintenance of motor function. This analysis showed that 16 ml of 0.1285 % ropivacaine is suitable for achieving differential block in ultrasound-guided axillary nerve block for hand and forearm surgery.

Bupivacaine‐induced cellular entry of QX‐314 and its contribution to differential nerve block

Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful.

Morphologic Abnormalities Are Poorly Predictive of Visceral Pain in Chronic Pancreatitis

Abdominal pain in chronic pancreatitis (CP) may be visceral or nonvisceral in origin. Differential nerve block (DNB) distinguishes visceral from nonvisceral pain. Endoscopic ultrasound and other imaging tests (eg, computed tomography and magnetic resonance cholangiopancreatography) are used to diagnose and stage CP. However, it is not known whether structural changes predict the presence of visceral pain, which may better respond to endoscopic, surgical, or visceral nerve interventions. We investigated the correlation of pancreatic structural abnormalities evident on imaging tests with the presence of visceral pain on DNB. A retrospective study was performed. Our DNB database was queried for patients who underwent imaging testing for evaluation of upper abdominal pain. The patients were classified into 3 groups based on structural severity: (1) normal pancreatic imaging, (2) mild CP, and (3) severe CP. The rates of visceral pain in the 3 groups were compared using a χ² test. Fifty-four patients were included. There was no significant difference in rates of visceral pain based on structural severity: 48% in normal, 60% in mild CP, 67% in severe CP (χ², P = 0.484). The severity of structural changes of CP found on imaging tests does not predict the presence of visceral pain.

A Role for Nociceptive, Myelinated Nerve Fibers in Itch Sensation

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents.

Su1366 The Severity of Structural Abnormalities on Endoscopic Ultrasound (EUS) Does Not Correlate With Visceral Pain in Chronic Pancreatitis (CP)

Abdominal pain in CP may arise from an inflamed parenchyma or obstructed pancreatic duct (visceral pain). However, many patients with CP have non-visceral pain sources (central, psychogenic, or somatosensory). EUS and other imaging tests (CT, MRCP) are used to diagnose and stage CP. However, it is not known whether structural changes on imaging tests predict the presence of visceral pain which may respond to “pancreas-directed” interventions (e.g. ERCP, surgical resection). The retrograde epidural differential nerve block (DNB) attempts to distinguish visceral from non-visceral pain.

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Transdermal Lidocaine Causes Differential Nerve Block through Distinct Manner from Spinal Administration

Transdermal Lidocaine Causes Differential Nerve Block through Distinct Manner from Spinal Administration

The antinociceptive and histologic effect of sciatic nerve blocks with 5% butamben suspension in rats.

Butamben, a lipophilic local anesthetic of the ester class, produces a differential nerve block of long duration. Epidural and peripheral nerve blocks with butamben, formulated as a 5%--10% suspension, result in prolonged analgesia without significant motor blockade. We evaluated the effect of butamben sciatic nerve block on antinociception using the rat paw formalin test, as well as withdrawal latencies to thermal stimulation, and assessed histologic changes in the nerve. After right sciatic nerve block with butamben 5% or saline, responses to intradermal injection of 5% formalin were recorded in randomly selected groups of 6 animals each on days 1, 2, 5, 10, 21, and 28. In an additional group of 8 thermal challenges to both hind paws were recorded at 1, 2, 5, 7, 10, 14, 17, 21, and 28 days after right sciatic butamben 5% blocks. Butamben injection decreased the formalin-induced flinches on days 2, 5, 10, 21 and 28 and decreased thermal challenges on days 1 through 17. Histologic changes were minimal. This study demonstrates a prolonged antinociceptive effect from butamben nerve block to both formalin-induced nociception and heat hyperalgesia, without an effect on gross motor function or histologic morphology. Butamben 5% nerve blocks produced a prolonged antinociceptive effect to formalin-induced nociception and heat hyperalgesia, without significant motor effect or evidence of substantial histologic changes.

What is the potential of studying receptor expression on nociceptors?

Since the early eighties we have witnessed a surge of major discoveries about mechanisms of a unique plasticity in the central nervous system (CNS) that play an important role in the generation of ongoing pain and hyperalgesia [17]. One spectacular example triggered by short periods of noci­ ceptive activity is the increased efficiency of synaptic transmission at pain-relevant neurons in the dorsal horn of the spinal cord [6,12]. These findings of central hyperexcitability have provided a great advance in our conceptual framework for the explanation of erstwhile enigmatic clinical symptoms such as touch-evoked pain (allodynia). Alterations of the CNS circuitry are also implicated in the consolidation of painful conditions that may persist, perhaps indefinitely, in some situations even in the absence of excitation of nociceptors. Al­ though it has been recognized for some time that changes in the receptive properties of nociceptors are the basis of some forms of hyperalgesia notably to heat [13], the impressive advances in the understanding of CNS plasticity have diverted attention from the periph­ eral events of nociception. It is therefore timely that the article by Carlton and Coggeshall refocuses on the peripheral aspects of nociception. In fact, several lines of evidence now show that changes in the excitability of primary nociceptive afferents may be the single most important factor in the generation and maintenance of acute inflammatory or chronic neuropathic pain in hu­ mans. Thus, local anesthetic blocks of affected nerves or tissues, differential nerve blocks, detailed psychophysi­ cal investigations, and intraneural recording and stimula­ tion experiments using microneurography all converge

Differential Nerve Block

Clinically, differential block is manifested by the loss of small fiber mediated sensation (e.g., temperature) two or more dermatomes beyond the sensory limit for large fiber mediated sensations. These observations support the belief that sensitivity to local anesthetics is inversely proportional to axon diameter. This study reports the first measurements of differential sensitivity to lidocaine in individual myelinated and unmyelinated mammalian dorsal root axons. Lumbar dorsal roots and vagus nerves were isolated from anesthetized adult rats and maintained in vitro in a perfusion/recording chamber at 37 +/- 0.3 degrees C. Using single fiber techniques, evoked action potentials in individual myelinated and unmyelinated axons were digitized and recorded for subsequent analysis. Axons were exposed to lidocaine at 150, 260, or 520 microM. Sensitivity to local anesthetic was assessed by measuring the incidence of conduction block and the magnitude of conduction velocity slowing under steady-state conditions. Data were obtained from 77 dorsal root axons and 41 vagal axons. The estimated steady-state EC50 lidocaine concentration for myelinated dorsal root axons (232 microM) was comparable to that for unmyelinated axons (228 microM). Similarly, the incidence of conduction block was not significantly different among dorsal root axon groups. However, unmyelinated dorsal root axons were significantly less sensitive to the conduction velocity slowing effect of lidocaine than their myelinated counterparts (P < 0.01). The incidence of conduction block in short (mean length 13.5 mm) dorsal root axons was not significantly different from that in long (mean length 22.4 mm) axons. Compared with dorsal root axons, the estimated EC50s for vagal myelinated and unmyelinated axons (345 and 285 microM, respectively), while lower were not significantly different. However, the incidence of conduction block at 260 microM lidocaine was significantly lower (16.7% vs. 56.7%; P < 0.05) in vagal myelinated axons. Although no difference in sensitivity to the conduction blocking effects of lidocaine could be demonstrated among dorsal root axons, myelinated axons were more sensitive to the conduction velocity slowing effects of lidocaine. This differential effect cannot explain clinical observations of differential nerve block. Differential sensory block with lidocaine may depend on factors (e.g., physiologic function) related only indirectly to individual axon conduction velocity (diameter).

The effect of local anaesthetics on TTX-resistant sodium channels in sensory ganglia of the rat

Local anaesthetics exert their effect by blocking the sodium channels in the peripheral nerve. In unmyelinated C-fibres however there is evidence that an additional type of sodium channel, the tetrodotoxin-resistant (TTX-R) Na+ channel [1] contributes to action potential propagation [2]. The different NA+ channels in different nerve fibres might be one explanation for differential nerve block induced by local anaesthetics. In this study the effects of local anaesthetics upon Dorsal Root Ganglia (DRG) TTX-R sodium channels were investigated. Table 11Table 11: (abstract 26). IC50-values for LA effect on TTX-resistant DRG sodium channels. Fitted values ± SEM. *IC50-values for C-fibre compound action potential block from [3]TTX-R Na+ currents of enzymatically dissociated adult rat DRG cells were investigated in 31 whole cell patches. The holding potential was set to − 100 mV and depolarizing pulses to −20 mV (5ms) were applied to elicit sodium currents. Experiments were carried out in 300 nM TTX-Ringer solution to block TTX-sensitive sodium currents. Local anaesthetics were applied externally. The temperature was 22°C in all experiments, external pH was adjusted to 7.4. A fitting method to assess phasic (use-dependent) block of sodium channels was developed. Concentration-inhibition curves for static block were derived for different local anaesthetics by quantifying for fractional peak sodium current block. Half-maximal inhibiting concentrations (IC50) were found by nonlinear least-squares fitting of the function B=c/(c + IC50) to data points and values are listed in the table. Results for the phasic block are not yet ready for publication in this abstract, but will be included in the presentation. This investigation gives a detailed study of local anaesthetic effects upon TTX-resistant sodium channels in mammalian sensory ganglia. Comparison of the TTX-R IC50 values with IC50 values for C-fibre block are surprisingly similar, whereas A fibres are already blocked at lower local anaesthetic concentrations [3]. Comparison of the observed effects with the effects upon TTX-sensitive channels of the same preparation (currently under investigation) should give more information about possible mechanisms of differential nerve block.

Noradrenaline-evoked pain in neuralgia

We have tested the effects of cutaneous application of noradrenaline in 35 patients presenting with neuropathic pain. Depending on the outcome of sympatholytic interventions the patients were considered to have sympathetically maintained pain (SMP; n = 25) or sympathetically independent pain (SIP; n = 10). Iontophoretic application or cutaneous injection of noradrenaline into symptomatic skin aggravated pain and mechanical or thermal hyperalgesia in 7 25 SMP patients. Results from differential nerve blocks suggested that noradrenaline-induced ongoing pain and heat hyperalgesia were signalled by unmyelinated afferents, while touch-evoked pain and cold hyperalgesia were signalled by myelinated afferents. In none of the remaining 18 25 SMP patients, 10 SIP patients or 18 normal subjects did application of noradrenaline result in any appreciable increase of pain. A follow-up of 12 patients (initially 9 SMP, 3 SIP) after 12–16 years showed that one individual (previously SMP) was healthy, while 3 patients still suffered from SMP and 8 from SIP. Of the 5 SMP patients who had noradrenaline-induced pain at the initial examination, only 1 SMP patient still responded to noradrenaline with pain and hyperalgesia. Three other patients had changed to SIP and 1 individual was healthy. None of these 4 and none of the 7 initially noradrenaline-unresponsive patients experienced pain to the noradrenaline challenge at follow-up. Thus, cutaneous noradrenaline application can aggravate the pain in some, but not all SMP patients. The abnormal noradrenaline reaction can change over time as can the pain relieving effects of sympatholytic therapy.

Neurologic Evaluation of the Rat during Sciatic Nerve Block with Lidocaine

Quantitative behavioral testing is necessary to establish a reproducible measure of differential functional blockade during regional anesthesia. Methods for assessment of the neurologic status (mental status, posture, gait, proprioception, motor function, autonomic function, and nociception) in veterinary neurology were adapted for the rat and used to monitor functional changes separately during a sciatic nerve block. Sprague-Dawley rats were acclimated to laboratory routine before the study so that lidocaine (0.1 ml, 1%) could be injected near the sciatic notch without any chemical restraint. The onset, duration, and magnitude of functional losses were monitored. Proprioceptive integrity was evaluated by assessing the response to tactile placing and the hopping response. Extensor postural thrust, a test for postural reactions in small animals, was assessed on a digital balance and found adequate for quantifying motor function. Analgesia was assessed by measuring withdrawal response latencies to noxious thermal stimulation (51 degrees C) and to superficial and deep noxious pinches. Autonomic function was monitored by measuring skin temperature. Contralateral limb function was used as an internal control, and injection of saline was used as an external control in separate, control animals. Onset of postural and gait abnormalities were observed as early as 40 s after injection. On each occasion proprioceptive impairment was detected first, followed by impairment of motor function and nociception. Complete absence of proprioception occurred from 10 to 30 min (n = 9) and of motor function at 30 min after injection (n = 10); both functions were fully recovered by 120 min. A unilateral increase in skin temperature on the foot was detected by 1 min; had reached its maximum change, 5.3 +/- 0.7 degrees C, at 10 min; and had returned to control levels at 60 min after injection (n = 12). Withdrawal response to cutaneous or superficial pain was absent in all ten animals from 5 to 30 min whereas the response to deep pain was absent in all ten animals at 20 min only. The response to noxious stimulation recovered at 90 min. Attention was paid to the temporal relation of the impairment of various functions. Quantitative observations of the onset, offset, and intensity of differential functional impairment or block over time will make it possible to establish the doses and conditions for local anesthetics that result in differential nerve block and will permit comparison of these changes among different drugs and "clinical" protocols.

Effect of Alkalinization on Differential Median Nerve Block with Lidocaine

Effect of Alkalinization on Differential Median Nerve Block with Lidocaine

Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain.

Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalgesia) is a hallmark of neuropathic and inflammatory pain states. Here we have examined the neural mechanisms that induce and maintain this component of mechanical hyperalgesia. The principle finding of these experiments is that the severity of brush-evoked pain correlates with the intensity of background pain in patients suffering from chronic painful neuropathies and in normal subjects with acute experimental chemogenic pain. In experiments on nine normal subjects topical application of mustard oil for 5 min evoked strong burning pain and hyperalgesia to light mechanical stimuli. Differential nerve blocks (by compression of the superficial radial nerve) revealed that the brush-evoked pain was transmitted by A beta-fibres, which normally encode non-painful tactile sensations, while the burning pain was signalled by C-fibres. Psychophysical measurements showed that mustard oil treatment resulted in a pronounced sensitization of nociceptors to heat so that subsequent innocuous changes of skin temperature from 35 to 40 degrees C resulted in a proportional increase of burning background pain. Changes in the magnitude of ongoing burning pain were closely correlated (r = 0.81) to the intensity of brush-evoked pain. While conduction block of A-fibres eliminated only touch-evoked pain, blockade of C-fibre excitation instantaneously abolished both ongoing and touch-evoked pain. In nine patients with chronic neuralgia (15 years mean duration) ongoing and brush-evoked pain were examined. In six patients, differential block of A beta-fibres eliminated touch-evoked pain, but ongoing pain persisted when only C-fibres were conducting. Complete relief of both ongoing and stimulus-induced pain was obtained in two patients with intravenous regional guanethedine block and in two other individuals by local anaesthetic blocks of nerves supplying the symptomatic skin, indicating that input from primary afferents was necessary for the maintenance of the pains and that ongoing pain was not self-perpetuated by central mechanisms alone. Quantitative sensory tests revealed heat hyperalgesia in four patients. In those individuals, an increase of skin temperature produced a graded increase of their ongoing pain which was closely correlated (r = 0.94) with the level of brush-evoked pain. In the remaining five patients there was no heat hyperalgesia and consequently no aggravation of pain by increases of skin temperature. Nevertheless when the intensity of the background pain fluctuated spontaneously there were also parallel changes (r = 0.88) of the severity of brush-evoked pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Different patterns of hyperalgesia induced by experimental inflammation in human skin.

Different types of hyperalgesia were studied after experimental induction of inflammation in small skin areas of healthy volunteers either by topical application of capsaicin solution (1% in 70% ethanol) or by briefly freezing a skin area of similar size to -28 degrees C. Sensory tests were performed 30 min after capsaicin application and 22 h after freeze lesions. Heat pain thresholds were lowered after both treatments, probably due to nociceptor sensitization. Hyperalgesia to four types of mechanical stimulation was studied. (i) Hyperalgesia to punctate stimuli was encountered at the skin site directly affected by the noxious chemical or freeze stimulus (1 degree zone) and in the surrounding skin (2 degrees zone) in both models though the area of 2 degrees hyperalgesia to punctate stimuli after freezing was smaller than after capsaicin. (ii) Hyperalgesia to gently brushing the skin was prominent after capsaicin in 1 degree and 2 degrees zone, but almost absent after freezing. It was concluded that both hyperalgesia to punctate stimuli and brush-evoked pain are due to central nervous plasticity changes rather than nociceptor sensitization. As revealed by differential nerve blocks, brush-evoked pain is mediated by low threshold mechanosensitive A beta-fibres, whilst hyperalgesia to punctate stimuli can be elicited when only C-fibres conduct. In contrast to hyperalgesia to punctate stimuli it requires continuous background discharges in nociceptor units. (iii) Pressure hyperalgesia to tonic stimulation with a blunt probe was encountered in the 1 degree zone of both types of inflammation and is probably due to recruitment of sensitized nociceptor units. (iv) Impact hyperalgesia was studied by shooting small bullets against the skin at predetermined velocities. It was found in the 1 degree zone after freezing and absent in the capsaicin model. Differential nerve blocks revealed that it is probably mediated by sensitized C-fibres. In conclusion, different types of inflammatory changes may result in characteristic different patterns of hyperalgesia.

The ability of humans to localise noxious stimuli

We have investigated the ability of humans to localise noxious stimuli on the dorsum of the hand. Pin-prick (non-penetrating needle prick), noxious heat (round 1 cm 2 copper probe heated to 50°C), mustard oil (100% applied topically in a small cotton ball, diameter 5 mm) and histamine (iontophoresis of 20 mC delivered to an area of 75 mm 2) were applied to skin with intact innervation and during a differential nerve compression block of the superficial radial nerve when only C-fibres were conducting. The mean mislocalisation (±S.E.M.; n = 8) of all stimuli was 9.5 ± 0.8 mm with normal nerve conduction and 8.9 ± 1.2 during the differential nerve block. There was no significant difference between the noxious submodalities. By contrast, when nerve conduction was intact, purely tactile stimulation (7 mN von Frey hair) was significantly better localised having a mean error of 5.5 ± 0.4 mm. We conclude that focal stimuli evoking itch or pain can be localised with high precision which is only marginally worse than for tactile stimuli. This suggests the existence of a somatotopical representation for noxious inputs in the brain similar to that found for tactile stimuli.

Dynamic and static components of mechanical hyperalgesia in human hairy skin

The principle finding of the present study is that there are two types of mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical hyperalgesia comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and a static component (hyperalgesia to pressure stimuli) signalled by unmyelinated afferents. While the static component is only found in the injured area, the dynamic component also extends into a halo of undamaged tissue surrounding the injury. The irritant chemicals, mustard oil or capsaicin, were applied transdermally in 20 subjects to a patch (2 × 2 cm) of hairy skin. Both substances evoked burning pain and hyperalgesia to mechanical stimuli. While stroking normal skin with a cotton bud was perceived only as touch prior to chemical stimulation, there was a distinctly unpleasant sensation afterwards. This component of mechanical hyperalgesia persisted for at least 30 min and was present in the skin exposed to the irritants (primary hyperalgesia) as well as in a zone of untreated skin surrounding the injury (secondary hyperalgesia) measuring 38 ± 4 cm 2 after capsaicin. Pressure pain thresholds dropped to 55 ± 8% of baseline level after mustard oil and to 46 ± 9% after capsaicin. However, this drop of thresholds was short-lived, lasting 5 min following mustard oil but persisting more than 30 min following capsaicin treatment. The reduction of pressure pain thresholds was only observed for treated skin areas, but not in the surrounding undamaged tissue from where brush-evoked pain could be evoked. When pressure pain thresholds were lowered, the pain had a burning quality which differed distinctly from the quality of brush-evoked pain. On-going burning pain and both types of mechanical hyperalgesia were critically temperature dependent. Mildly cooling the skin provided instant relief from on-going pain, abolished brush-evoked pain and normalized pressure pain thresholds. Rewarming resulted in a reappearence of on-going pain and hyperalgesia. The effect of a nerve compression block of the superficial radial nerve on these sensations was tested in 14 experiments. When the ability to perceive light touch had been abolished, there was also no touch-evoked pain, indicating that this component of mechanical hyperalgesia is mediated by large-diameter primary afferents. At a later stage of the block when the subjects' ability to perceive cold stimuli had also been lost, application of cool stimuli still eliminated on-going burning pain, suggesting that pain relief afforded by cooling the skin acts at the peripheral receptor level and not by central masking. Importantly, at this stage of the block, when only unmyelinated primary afferents conducted, neither spontaneous pain, nor hyperalgesia to heat, nor the lowered pressure pain threshold had changed significantly. Based on the differences in quality of sensations, in spatial and temporal profiles and in susceptibility to differential nerve blocks, we conclude that irritant chemicals induce a dynamic and static component of mechanical hyperalgesia signalled by large-diameter or unmyelinated fibres, respectively. While the static component may be mediated by sensitized peripheral nociceptors, the dynamic component is probably the consequence of an altered processing of large diameter primary afferent input in the central nervous system subsequent to a maintained barrage of nociceptor activity. The parallel fluctuation of brush-evoked and burning background pain therefore suggest that on-going activity from nociceptors is required to maintain a central state that permits dynamic mechanical hyperalgesia to be expressed in humans.