An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol

Background  

Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP), remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain.     

Intravenous Lidocaine Relieves Spinal Cord Injury Pain: A Randomized Controlled Trial

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing.

Results: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction >= 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick.     

Activation of glial cells in the spinal cord of a model of lumbar radiculopathy

Purpose  

Glial cells in the spinal cord of a lumbar radiculopathy model were investigated using immunohistochemical methods. Neuropathic pain is a consequence of neural plasticity. In models of neuropathic pain models, roles for glial cells in the development of pain behaviors have been reported. Accumulating evidence suggests that activation of p38 mitogen-activated protein kinase (p38) in glial cells contributes to the pathogenesis of neuropathic pain. We examined whether activation of glial cells is involved in the development of neuropathic pain-like behavior observed in a model of lumbar radicular pain that we developed. However, the pathogenesis of lumbar radiculopathy and in particular the effect of spinal glial activation on pain transmission in the dorsal horn of the spinal cord are still not fully known.     

Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial

BACKGROUND: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine. METHODS: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing. RESULTS: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction > or = 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick. CONCLUSIONS: Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain. Results are consistent with a central-acting effect of sodium channel blockers acting on neuronal hyperexcitability. Agents (such as anticonvulsants or antiarrhythmics) with sodium channel-blocking properties may be a treatment option for spinal cord injury pain.     

Long-term exposure to local but not inhalation anesthetics affects neurite regeneration and synapse formation between identified lymnaea neurons

BACKGROUND: General and local anesthetics are used in various combinations during surgical procedures to repair damaged tissues and organs, which in almost all instances involve nervous system functions. Because synaptic transmission recovers rapidly from various inhalation anesthetics, it is generally assumed that their effects on nerve regeneration and synapse formation that precede injury or surgery may not be as detrimental as that of their local counterparts. However, a direct comparison of most commonly used inhalation (sevoflurane, isoflurane) and local anesthetics (lidocaine, bupivacaine), vis-a-vis their effects on synapse transmission, neurite regeneration, and synapse formation has not yet been performed. METHODS: In this study, using cell culture, electrophysiologic and imaging techniques on unequivocally identified presynaptic and postsynaptic neurons from the mollusc Lymnaea, the authors provided a comparative account of the effects of both general and local anesthetics on synaptic transmission, nerve regeneration, and synapse formation between cultured neurons. RESULTS: The data show that clinically used concentrations of both inhalation and local anesthetics affect synaptic transmission in a concentration-dependent and reversal manner. The authors provided the first direct evidence that long-term overnight treatment of cultured neurons with sevoflurane and isoflurane does not affect neurite regeneration, whereas both lidocaine and bupivacaine suppress neurite outgrowth completely. The soma-soma synapse model was then used to compare the effects of both types of agents on synapse formation. The authors found that local but not inhalation anesthetics drastically reduced the incidence of synapse formation. The local anesthetic-induced prevention of synapse formation most likely involved the failure of presynaptic machinery, which otherwise developed normally in the presence of both sevoflurane and isoflurane. CONCLUSION: This study thus provides the first comparative, albeit preclinical, account of the effects of both general and local anesthetics on synaptic transmission, nerve regeneration, and synapse formation and demonstrates that clinically used lidocaine and bupivacaine have drastic long-term effects on neurite regeneration and synapse formation as compared with sevoflurane and isoflurane.     

Differential Effect of Ketamine and Lidocaine on Spontaneous and Mechanical Evoked Pain in Patients with Nerve Injury Pain

Background: The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ketamine, an N-methyl-d-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain.

Methods: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion.

Results: Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains.     

Anti-hyperalgesic effect of CaMKII inhibitor is associated with downregulation of phosphorylated CREB in rat spinal cord

Purpose  

Calcium/calmodulin-dependent protein kinase (CaMK) II and its downstream effector cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB) may be involved in the development of neuropathic pain. The aim of this study was to examine the effect of the CaMKII inhibitor AIP on the association of CaMKII and CREB in a partial sciatic nerve ligation neuropathic pain model in rats.     

Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia

Background

Lidocaine has been used as a local anesthetic with anti-inflammatory properties, but its effects on neuroinflammation have not been well defined. In the present study, we investigated the prophylactic effects of lidocaine on lipopolysaccharide (LPS)-activated microglia and explored the underlying mechanisms.

Materials and methods

Microglial cells were incubated with or without 1 μg/mL LPS in the presence or absence of lidocaine, a p38 mitogen–activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), or small interfering RNA. The protein and expression levels of inflammatory mediators, such as monocyte chemotactic protein 1, nitric oxide, prostaglandin E₂, interleukin 1β, and tumor necrosis factor α were measured using enzyme-linked immunosorbent assays and real-time polymerase chain reaction. The effect of lidocaine on NF-κB and p38 MAPK activation was evaluated using enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic mobility shift assay.

Results

Lidocaine (≥2 μg/mL) significantly inhibited the release and expression of nitric oxide, monocyte chemotactic protein 1, prostaglandin E₂, interleukin 1β, and tumor necrosis factor α in LPS-activated microglia. Treatment with lidocaine also significantly inhibited the phosphorylation of p38 MAPK and the nuclear translocation of NF-κB p50/p65, increased the protein levels of inhibitor kappa B-α. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by SB203580, pyrrolidine dithiocarbamate, and small interfering RNA.

Conclusions

Prophylactic treatment with lidocaine inhibits LPS-induced release of inflammatory mediators from microglia, and these effects may be mediated by blockade of p38 MAPK and NF-κB signaling pathways.     

Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron

Purpose  

Although lidocaine-induced cell toxicity has been reported, its mechanism is unclear. Cell size, morphological change, and membrane resistance are related to homeostasis and damage to the cell membrane; however, the effects of lidocaine on these factors are unclear. Using an identified LPeD1 neuron from Lymnaea stagnalis, we sought to determine how lidocaine affects these factors and how lidocaine is related to damage of the cell membrane.     

A ação analgésica da lidocaína intravenosa no tratamento da dor crônica: uma revisão de literatura

BackgroundPain is a public health problem, greatly impairing quality of life. Almost 80% of patients with chronic pain reported that their pain interferes with activities of daily living, and two thirds reported that the pain causes negative impact on their personal relationships. The physical and functional disability, whether temporary or permanent, compromises the professional activity and causes work absenteeism, increasing costs of health systems.ObjectivesThe aim of this review is to analyze, based on the literature, the analgesic effect of lidocaine administered intravenously for the treatment of chronic pain and to evaluate the reduction of pain intensity in patients with chronic pain, focusing on musculoskeletal and neuropathic etiology.MethodologyThe method used was a review of the literature, consisting in searching the scientific literature on the efficacy of intravenous lidocaine infusion in the treatment of patients with chronic pain.ContentOf the 19 studies reviewed, 12 had results that confirm the analgesic effect of intravenous lidocaine in patients with chronic pain. Most authors used doses of 5 mg/kg infused for 30 minutes or more, producing significant analgesia with variable duration (minutes to weeks).ConclusionsBased on the literature review, it is not possible to uniformly specify the most effective and safe dose of lidocaine administered intravenously for the treatment of neuropathic or musculoskeletal pain. As for effectiveness, the intravenous infusion of lidocaine as an alternative for the treatment of chronic pain of various etiologies seems very promising, but further studies need to be conducted.     

Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II

BACKGROUND: Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II. METHODS: This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli. RESULTS: Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level. CONCLUSIONS: This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli.     

Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain

Background  

The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms.     

Local anesthetics suppress nerve growth factor-mediated neurite outgrowth by inhibition of tyrosine kinase activity of TrkA

Local anesthetics (LAs) suppress sympathetic sprouting, which correlates with neuropathic pain. However, the precise mechanism of the suppression is unknown. Nerve growth factor (NGF) contributes to the sympathetic sprouting, and NGF signaling starts with NGF-stimulated autophosphorylation of TrkA, which is a high affinity receptor of NGF. We examined the effects of lidocaine, bupivacaine, and procaine on NGF signaling under suppression of NGF-stimulated neurite outgrowth in PC12 cells, which is a cellular model of sympathetic sprouting. To investigate the effect of these LAs on NGF-mediated neurite outgrowth of PC12 cells, cells were incubated with 40, 400, and 4000 microM of each LA. The effect of LAs on NGF-stimulated TrkA activity was examined to analyze autophosphorylation of TrkA using immunoprecipitation and immunoblotting. Cytotoxic effects of LAs on PC12 cells were also assessed by lactate dehydrogenase release and by propidium iodide staining. Lidocaine (400 microM), bupivacaine (40 and 400 microM), or procaine (4000 microM) suppressed either neurite outgrowth or autophosphorylation significantly without cytotoxicity. The inhibition of NGF-stimulated tyrosine kinase activity of TrkA might be involved in the mechanisms of suppression of neurite outgrowth induced by LAs.     

Subanalgesic ketamine enhances morphine-induced antinociceptive activity without cortical dysfunction in rats

Purpose

Ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, has been used for the treatment of cancer pain as an analgesic adjuvant to opioids. However, ketamine is known to produce psychotomimetic side effects including cognitive impairments under a high-dose situation, presumably as the result of cortical dysfunction. Here, we investigated whether low-dose ketamine was useful as an analgesic adjuvant to morphine for pain control, focusing on frontocortical function.

Methods

To assess the analgesic effects of ketamine with or without morphine, we performed behavioral and histochemical experiments, using the hot plate test and c-Fos expression analysis in rats. The effect on cortical function was also determined by prepulse inhibition (PPI) of the acoustic startle and evoked potentials in the hippocampal CA1-medial prefrontal cortex (mPFC) synapses as measures of synaptic efficacy.

Results

Coadministration of ketamine as a subanalgesic dose significantly enhanced intraperitoneal morphine-induced antinociceptive response, which was measured as the increased reaction latency in the hot plate test. In addition, the noxious thermal stimulus-induced c-Fos expression in the ventrolateral periaqueductal gray matter was significantly suppressed by concomitant ketamine and morphine. In contrast, the subanalgesic dose of ketamine did not impair PPI and synaptic efficacy in the mPFC.

Conclusion

The present results indicate that the morphine-induced analgesic effect is enhanced by a concomitant subanalgesic dose of ketamine without affecting cortical function. Our findings possibly support the clinical notion that low-dose ketamine as an analgesic adjuvant has therapeutic potential to reduce opioid dosage, thereby improving the quality of life in cancer pain patients.     

Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain

Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states. IMPLICATIONS: Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.     

The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45 degrees C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia. Implications: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.     

Activation of satellite cells in the dorsal root ganglia in a disc-punctured rat model

Background  

The neural mechanisms underlying discogenic low back pain caused by disc degeneration remain unclear. Previous studies demonstrated that satellite cells (SC) play an important role in neuropathic pain.     

The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety

Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk-benefit ratio of i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre-existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a ‘high-risk’ medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri-operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg^-1, calculated using the patient’s ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg^-1.h^-1 for no longer than 24 h is recommended, subject to review and re-assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.     

Concentration-Effect Relationship of Intravenous Lidocaine on the Allodynia of Complex Regional Pain Syndrome Types I and II

Background: Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II.

Methods: This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 [mu]g/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli.

Results: Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level.     

Analgesic effect of intravenous ATP on postherpetic neuralgia in comparison with responses to intravenous ketamine and lidocaine

Purpose No study has been performed on the analgesic effect of adenosine 5-triphosphate (ATP) on postherpetic neuralgia (PHN). We conducted an open-label trial of ATP in patients with PHN, and compared ATP with ketamine and lidocaine.Methods Twelve patients with PHN were studied. On separate days, ketamine (0.3mg·kg^–1), lidocaine (2mg·kg^–1), and ATP (100µg·kg^–1·min^–1 or less for 120min) were administrated intravenously. The intensity of spontaneous pain as well as tactile allodynia was assessed using a visual analog scale (VAS). When the VAS score for spontaneous pain was decreased by more than 50%, the patient was classified as a responder.Results Five, 6, and 6 patients responded to ketamine, lidocaine, and ATP, respectively. In 6 ATP responders, pain relief developed slowly and lasted for 9 (median) h (range: 3–72h). All 5 ketamine responders and only 1 of 7 ketamine nonresponders responded to ATP (5/5 vs 1/7, P < 0.05, ² test) whereas 2 of 6 responders to lidocaine and 4 of 6 nonresponders to lidocaine responded to ATP (2/6 vs 4/6, P > 0.05). The ketamine responders responded to ATP more often than did the lidocaine responders (5/5 vs 2/6, P < 0.05).Conclusion Intravenous ATP exerted slowly developing and long-lasting analgesic effects in half of patients with PHN. Patients with ketamine-responsive PHN were likely to respond to ATP.