Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Metanálise como Assunto , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/normas , Projetos de Pesquisa/normas , Interpretação Estatística de Dados , Resistência a Medicamentos/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicina Baseada em Evidências , Humanos , Variações Dependentes do Observador , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. METHODS: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. RESULTS: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. CONCLUSION: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.
Assuntos
Cannabis , Infecções por HIV/complicações , Doenças do Sistema Nervoso Periférico/terapia , Doenças do Sistema Nervoso Periférico/virologia , Fitoterapia , Transtornos de Sensação/terapia , Transtornos de Sensação/virologia , Afeto , Cannabis/efeitos adversos , Feminino , Temperatura Alta , Humanos , Hiperalgesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Manejo da Dor , Cuidados Paliativos , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/psicologia , Estimulação Física , Transtornos de Sensação/fisiopatologia , Transtornos de Sensação/psicologia , FumarRESUMO
In this randomized pilot clinical trial, the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium. Postoperative delirium occurred in 5/12 patients (42%) who received placebo vs 0/9 patients who received gabapentin, p = 0.045. The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin.
Assuntos
Aminas/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Delírio/etiologia , Delírio/prevenção & controle , Procedimentos Neurocirúrgicos/efeitos adversos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Pré-Medicação/métodos , Ácido gama-Aminobutírico/uso terapêutico , Analgésicos/uso terapêutico , Estudos de Viabilidade , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Projetos Piloto , Efeito Placebo , Coluna Vertebral/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Nerve injury results in increases in spinal glutamate, which opens the NMDA ionophore channel, causing an influx of calcium. A glycine-binding site must be occupied for the channel to open. GV196771 is a selective antagonist of the glycine-binding site of the NMDA ionophore. OBJECTIVE: To determine the efficacy of GV196771 in subjects with chronic neuropathic pain in a proof-of-concept study. METHODS: With informed consent, 63 subjects (31 placebo, 32 GV196771) with neuropathic pain (diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, or peripheral nerve injury), a visual analogue score averaging > or =30 mm during the screening period, and a well-defined primary area of mechanical allodynia were recruited for the study. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study design was utilized. Subjects came to the research center for a total of five visits over a 21-day period, which consisted of a 14-day treatment period followed by a 7-day washout period. Spontaneous and evoked pain scores, mechanical sensory testing, quantitative sensory testing, Short Form McGill Pain Questionnaire, patient global satisfaction, and safety assessments were made during the study. RESULTS: There was no significant effect of GV196771 on spontaneous or evoked pain, quantitative sensory testing, or patient global satisfaction. There was a significant effect of GV196771 on the area of dynamic and static allodynia on days 7 and 14. The overall incidence of adverse events during treatment was similar for GV196771 (56%) and placebo (71%). The incidence of drug-related adverse events during treatment was higher for placebo (42%) than GV196771 (28%). CONCLUSIONS: Although the glycine antagonists show anti-hyperalgesic action in animal models of neuropathic pain, GV196771 does not appear to be an effective treatment in subjects with chronic neuropathic pain. This may be due to insufficient penetration of GV196771 to central sites of action, differences between the human and animal glycine receptors, or differences between neuropathic pain in animal models and humans.
Assuntos
Glicinérgicos/uso terapêutico , Glicina/antagonistas & inibidores , Indóis/uso terapêutico , Dor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Glicinérgicos/administração & dosagem , Temperatura Alta , Humanos , Indóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor/efeitos dos fármacos , Satisfação do Paciente , Doenças do Sistema Nervoso Periférico/complicações , Pirróis/administração & dosagem , Limiar Sensorial/efeitos dos fármacos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Adenosine is an endogenous compound that may have analgesic effects. Results from clinical trials are not consistent, however, and there is a need for large-scale, randomized, placebo-controlled studies to clarify the role of adenosine in the treatment of pain states, including acute nociceptive pain and pain involving central sensitization. METHODS: The analgesic and antihyperalgesic effect of systemic adenosine on the heat/capsaicin sensitization model of experimental pain was investigated in 25 healthy human volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 minutes, followed by a 30-minute application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin to 40 degrees C for 5 minutes at 40-minute intervals. Subjects received intravenous adenosine 60 microg/kg/min or saline for 85 minutes. Areas of secondary hyperalgesia to von Frey hair and brush stimulation, heat-pain detection thresholds (HPDTs) in normal and sensitized skin, and painfulness of stimulation with 45 degrees C for 1 minute (LTS) in normal skin were quantified before, during, and after study drug infusion. RESULTS: Systemic adenosine had no effect on the area of secondary hyperalgesia to von Frey hair or brush stimulation, HPDT in normal or sensitized skin, or painfulness of LTS in normal skin. CONCLUSION: We conclude that adenosine has no effect on acute nociceptive pain induced by heat stimulation or on secondary hyperalgesia induced by heat/capsaicin sensitization in healthy volunteers.
Assuntos
Adenosina/uso terapêutico , Capsaicina/farmacologia , Hiperalgesia/tratamento farmacológico , Dor/tratamento farmacológico , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adulto , Temperatura Alta , Humanos , Injeções Intravenosas , Masculino , Limiar da Dor/efeitos dos fármacosRESUMO
We investigated the effects of i.v. magnesium on secondary hyperalgesia following heat/capsaicin stimulation in human volunteers. Twenty-five volunteers were included in this double blind, randomized, crossover study. Sensitization was induced in the volunteers, who were then subjected to either i.v. saline or magnesium sulphate. No analgesic or antihyperalgesic effect could be demonstrated in sensitized skin during infusion of magnesium. In contrast, painfulness of thermal stimulation was increased in normal skin. These results suggest that i.v. magnesium has no important analgesic effects in clinically relevant doses.
Assuntos
Analgésicos/uso terapêutico , Capsaicina/efeitos adversos , Temperatura Alta/efeitos adversos , Magnésio/uso terapêutico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Humanos , Infusões Intravenosas , Masculino , Modelos Biológicos , Dor/etiologia , Pele , Falha de TratamentoRESUMO
BACKGROUND: The heat--capsaicin sensitization model was developed as a noninvasive and noninjurious human experimental pain model. The sequential application of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat--capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-associated measures was tested with remifentanil, a potent and ultrashort acting mu-opioid agonist. METHODS: Sensitization was induced by heating forearm skin with a thermode at 45 degrees C for 5 min, immediately followed by application of 0.075% capsaicin cream for 30 min. Sensitization was rekindled four times at 40-min intervals with the thermode at 40 degrees C for 5 min. After each rekindling, areas of secondary hyperalgesia were measured, and the painfulness of thermal stimulation in normal skin with 45 degrees C for 1 min (long thermal stimulation [LTS]) was rated. Before and during the second rekindling, remifentanil 0.10 microg x kg(-1) x min(-1) or saline-placebo was infused for 35 min. RESULTS: Infusion of remifentanil reduced the areas of secondary hyperalgesia to 29--30% of baseline size compared with 75--83% during placebo. Similarly, remifentanil reduced the painfulness of LTS to 29% of baseline severity compared with 84% during placebo. Areas of secondary hyperalgesia and LTS painfulness returned to baseline levels by the time of the third rekindling, demonstrating rapid disappearance of remifentanil analgesia and possibly transient spontaneous opioid withdrawal hyperalgesia. CONCLUSION: Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.
Assuntos
Analgésicos Opioides/uso terapêutico , Capsaicina/efeitos adversos , Hiperalgesia/tratamento farmacológico , Piperidinas/uso terapêutico , Adulto , Feminino , Temperatura Alta/efeitos adversos , Humanos , Hiperalgesia/etiologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , RemifentanilRESUMO
OBJECTIVE: To assess the efficacy, tolerability, and safety of riluzole in the treatment of peripheral neuropathic pain conditions. BACKGROUND: Both basic and clinical research has demonstrated that drugs with sodium channel and NMDA antagonism can be effective in alleviating neuropathic pain. Riluzole, a drug currently used for treatment of ALS, possesses these properties. It was hypothesized that riluzole would be effective in reducing the pain in subjects with peripheral neuropathic pain. METHODS: Two randomized, placebo-controlled, crossover studies were performed at two sites. Study 1 compared 100 mg/day of riluzole (the currently recommended dosage for treatment of ALS) versus placebo, and Study 2 compared 200 mg/day of riluzole versus placebo. Each treatment phase (both studies) was 2 weeks long, separated by 2-week wash-out periods. Outcome measures included change in the score on a 100-mm pain intensity visual analog scale, the Neuropathic Pain Scale, allodynia, hyperalgesia, and preference for study treatment phase. RESULTS: Twenty-two subjects completed Study 1, and 21 subjects completed Study 2. Four subjects (two from each study) discontinued the study because of intolerable side effects. No statistical difference was found for any study outcome measure between riluzole and placebo for either study. In Study 1, pain intensity was more likely to increase than decrease with riluzole (mean treatment difference 8.7 mm; 95% CI -19.5 to +2.1 mm). In Study 2, very slight pain reduction was observed with riluzole compared with placebo (mean treatment difference 1.4 mm; 95% CI -5.1 to +8.0 mm). In both studies, the majority of subjects chose "no change" in pain on the category relief scale after placebo and riluzole treatment phases. On study completion, no treatment preference was reported by 76% of the subjects in Study 1 and by 61% of the subjects in Study 2. CONCLUSIONS: Doses of riluzole at (100 mg) or above (200 mg) those used for the treatment of ALS were not effective in alleviating peripheral neuropathic pain.
Assuntos
Dor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Riluzol/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Riluzol/administração & dosagemRESUMO
UNLABELLED: 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.
Assuntos
Anestésicos Locais/uso terapêutico , Capsaicina/efeitos adversos , Temperatura Alta/efeitos adversos , Hiperalgesia/tratamento farmacológico , Lidocaína/uso terapêutico , Dor/tratamento farmacológico , Adulto , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Estudos Cross-Over , Tontura/induzido quimicamente , Método Duplo-Cego , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/etiologia , Infusões Intravenosas , Injeções Intravenosas , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Masculino , Nociceptores/efeitos dos fármacos , Dor/induzido quimicamente , Dor/etiologia , Medição da Dor , Limiar da Dor , Placebos , Pele/inervação , Fases do Sono/efeitos dos fármacos , Transtornos da Visão/induzido quimicamente , Xerostomia/induzido quimicamenteRESUMO
For neuropathic pain, there is evidence that the analgesic effect of intravenous sodium-channel blockers is robust and dose dependent. Oral agents are less impressive, but efficacious nonetheless, especially at higher doses. Despite the evidence from animal studies for a role of sodium channels in inflammatory hyperalgesia, the clinical evidence of analgesic effect of oral and intravenous sodium channel blockers in both acute and chronic nonneuropathic pain is equivocal. The results to date from human experimental pain models suggest a lack of effect of systemic lidocaine on acute nociceptive pain and that the effect on cutaneous hyperalgesia is modest, at best. Furthermore, the literature suggests that the systemic lidocaine analgesia is both dose and diagnosis dependent.
RESUMO
A gas chromatographic method for the determination of levorphanol in human plasma is described. The method utilizes extractive alkylation with tetrabutylammonium cation as the phase-transfer catalyst and pentafluorobenzyl bromide as the alkylating agent, and employs a structural analog, d-3-hydroxy-N-ethylmorphinan, as the internal standard. The pentafluorobenzyl ethers formed are separated by capillary gas chromatography and detected by electron capture. The method has good precision and accuracy for concentrations ranging from 0.25 ng/ml to 100 ng/ml and has been used to measure plasma concentrations as part of a study to evaluate the management of chronic neuropathic pain with levorphanol.
Assuntos
Analgésicos Opioides/sangue , Cromatografia Gasosa/métodos , Levorfanol/sangue , Calibragem , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The heat/capsaicin sensitization model is a new human experimental pain model that synergistically combines non-invasive physical and chemical methods of nociceptor stimulation to produce stable and long-lasting hyperalgesia with a low potential for skin injury. In 10 healthy volunteers the forearm was stimulated with a 45 degrees C thermode for 5 min to produce an area of secondary hyperalgesia. Applying capsaicin cream for 30 min further expanded the area of secondary hyperalgesia. Periodically heating the treated skin with a previously non-painful temperature of 40 degrees C re-kindled the sensitization enough to maintain stable areas of secondary hyperalgesia for 4h. The evoked pain was moderate and well tolerated. The heat/capsaicin sensitization model should be well suited for studying pain mechanisms and testing new analgesics.
Assuntos
Capsaicina/efeitos adversos , Temperatura Alta , Hiperalgesia/etiologia , Modelos Biológicos , Dor/etiologia , Adulto , Feminino , Humanos , Masculino , Valores de ReferênciaRESUMO
Capsaicin, which has been studied extensively as a treatment for itch and several chronic pain disorders, induces burning during the first week of therapy, causing a substantial percentage of patients to discontinue treatment prematurely. We examined whether pre-treatment with the topical anesthetic EMLA reduces the burning sensation induced by capsaicin and alters capsaicin effects on thermal sensation and pain thresholds. Healthy adult volunteers participated in the single-blind, 6-day study. After baseline measurement of warmth, cold pain and heat pain thresholds with a computerized thermal sensory analyzer, subjects applied EMLA thrice daily on one forearm and vehicle placebo on the other forearm, 60 min before applying capsaicin 0.075% on both forearms. Subjects rated burning sensations 3 times a day throughout the study. After 1 and 5 days of thrice daily application of EMLA or vehicle followed by capsaicin, thermal sensory testing was repeated. Subjects rated burning sensations to the significantly less on the EMLA pre-treated forearm compared with the placebo pre-treated forearm during all 5 days of treatment (p < 0.01). Capsaicin with and without EMLA produced significant heat pain hyperalgesia and cold pain hypoalgesia after 1 day of treatment. After 5 days of treatment, heat pain hyperalgesia persisted on both forearms; however, it was significantly less on the EMLA-treated forearm vs the vehicle-treated site (p < 0.03). Cold pain hypoalgesia persisted in both forearms. The warmth sensation threshold was significantly higher on the EMLA-pre-treated forearm after 1 and 5 days of treatment. In conclusion, pre-treatment with EMLA significantly reduced the burning sensation from capsaicin and attenuated heat hyperalgesia during treatment.
Assuntos
Anestésicos Locais/farmacologia , Capsaicina/efeitos adversos , Hiperalgesia/prevenção & controle , Lidocaína/farmacologia , Limiar da Dor/efeitos dos fármacos , Parestesia/prevenção & controle , Pré-Medicação , Prilocaína/farmacologia , Administração Cutânea , Adulto , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Hiperalgesia/induzido quimicamente , Lidocaína/administração & dosagem , Combinação Lidocaína e Prilocaína , Masculino , Pessoa de Meia-Idade , Parestesia/induzido quimicamente , Prilocaína/administração & dosagem , Valores de Referência , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do TratamentoRESUMO
The study goal was to determine the half-life elimination of cocaine and benzoylecgonine (BZE) in the newborn. Three 0.3-mL blood samples were collected during the first day of life. Urine was collected once daily. Cocaine and BZE concentrations were determined by gas chromatography-mass spectrometry. An extraction method was developed for measuring low concentrations of cocaine and BZE in small (0.1 mL) blood samples. Cocaine had a half-life of 11.6 h in one subject. The half-life of BZE during the first day of life, based on blood data in 13 subjects, was 16 h (95% confidence interval [CI], 12.8 to 21.4 h). The half-life of BZE during the first week of life, based on urine data in 16 subjects, was 11.2 h (95% CI, 10.1 to 11.8 h). The novel extraction method for small blood sample volumes should be applicable to other basic drugs.
Assuntos
Técnicas de Química Analítica/métodos , Cocaína/análogos & derivados , Cocaína/metabolismo , Recém-Nascido , Cocaína/sangue , Cocaína/farmacocinética , Cocaína/urina , Feminino , Sangue Fetal/química , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , GravidezRESUMO
Postherpetic neuralgia (PHN) is a neuropathic pain disorder that occurs most often in the elderly. This painful condition is uniquely suited for clinical research, resulting in an emerging understanding of the pathophysiology of the persistent pain. Until recently, only the tricyclic antidepressants proved effective for PHN. Controlled trials of a wide variety of therapeutic strategies are in progress or have been recently completed.
Assuntos
Herpes Zoster/diagnóstico , Neuralgia/diagnóstico , Medição da Dor , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Antidepressivos Tricíclicos/efeitos adversos , Antidepressivos Tricíclicos/uso terapêutico , Ensaios Clínicos como Assunto , Herpes Zoster/tratamento farmacológico , Humanos , Neuralgia/tratamento farmacológicoRESUMO
The objective of this study was to measure the umbilical cord plasma levels of cocaine, nicotine, caffeine, and their metabolites. Thirty-six neonates at risk for prenatal cocaine exposure were prospectively enrolled. Umbilical cord plasma was analyzed by gas chromatography-mass spectroscopy for cocaine, cocaethylene, benzoylecgonine (BZE), nicotine, cotinine, and caffeine. Eighteen neonates were plasma positive for BZE, and 50% of these were also positive for cocaine. Cocaethylene was not found. The maximum plasma cocaine concentration was 88 ng/mL (mean, 39 ng/mL). The maximum plasma BZE concentration was 3880 ng/mL (mean, 844 ng/mL). Among BZE-positive babies, the mean plasma drug levels were as follows: nicotine, 1.8 ng/mL; cotinine, 94 ng/mL; and caffeine, 1205 ng/mL. Among the BZE-negative babies, the mean plasma drug levels were as follows: nicotine, 5.2 ng/mL; cotinine, 97 ng/mL; and caffeine, 1440 ng/mL. These cocaine levels raise the possibility of pharmacological effects of cocaine in the early neonatal period.
Assuntos
Cafeína/sangue , Cocaína/sangue , Sangue Fetal , Nicotina/sangue , Cafeína/urina , Cocaína/análogos & derivados , Cocaína/urina , Cotinina/sangue , Cotinina/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Recém-Nascido , Nicotina/urina , Estudos Prospectivos , São Francisco , Detecção do Abuso de Substâncias/métodosRESUMO
Patients with acute herpes zoster, and to a lesser extent post-herpetic neuralgia (PHN), have been reported to respond to local anesthetic blockade of the sympathetic nervous system. In animal models of nerve injury, local injection of adrenergic agonists after nerve injury, but not before, excites nociceptors. In some patients with chronic neuropathic pain, local application of norepinephrine evokes pain. In 15 subjects with PHN, the role of adrenergic receptors in PHN pain was assessed in a two-session double blind study comparing the response to cutaneous infiltration of epinephrine or phenylephrine (30 micrograms in 3 ml) with the response to normal saline in both the painfully affected skin and mirror-image normal skin. Two adjacent sites were studied on each side of the body, one site for injection and the other for measuring sensory effects of the injection. In the morning part of each session, mirror-image normal skin was injected. In the afternoon portion of each session, skin in the most painful area affected by PHN was injected. Injection of saline or the adrenergic agonist in normal skin produced mild and transient pain without development of allodynia and without affecting overall PHN pain intensity. In PHN skin, injection of saline and the adrenergic agonist produced an equivalent degree of transient pain that was slightly greater than injection into mirror-image normal skin. After injection of the adrenergic agonist into PHN skin, both overall PHN pain and allodynia severity were significantly greater than after saline injection, peaking at 10-15 min post-injection. Even when PHN has been present for years, adrenergic receptor stimulation in PHN skin increases pain, most likely through direct activation of C-nociceptors in the painful skin. Increased allodynia is most likely mediated centrally and driven by the increase in C-nociceptor input.