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OBJECTIVE: To determine if a 4-week manual therapy treatment restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain (NSCNP), as well as the existence of a possible relationship between changes in pain processing mechanisms and clinical outcome. DESIGN: Cohort study. METHODS: Sixty-three patients with NSCNP, comprising 79% female, with a mean age of 45.8 years (standard deviation: 14.3), received four treatment sessions (once a week) of manual therapy including articular passive mobilizations, soft tissue mobilization and trigger point treatment. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and temporal summation of pain (TSP) were evaluated at baseline and after treatment completion. Therapy outcome was measured using the Global Rating of Change Scale (GROC), the Neck disability Index (NDI), intensity of pain during the last 24 hours, Tampa Scale of Kinesiophobia (TSK) and Pain Catastrophizing Scale (PCS). Two sets of generalized linear mixed models with Gaussian response and the identity link were employed to evaluate the effect of the intervention on clinical, psychological and psychophysical measures and the association between psychophysical and clinical outcomes. RESULTS: Following treatment, an increased CPM response (Coefficient: 0.89; 95% credibility interval = 0.14 to 1.65; P = .99) and attenuated TSP (Coefficient: -0.63; 95% credibility interval = -0.82 to -0.43; P = 1.00) were found, along with amelioration of pain and improved clinical status. PPTs at trapezius muscle on the side of neck pain were increased after therapy (Coefficient: 0.22; 95% credibility interval = 0.03 to 0.42; P = .98), but not those on the contralateral trapezius and tibialis anterior muscles. Only minor associations were found between normalization of TSP/CPM and measures of clinical outcome. CONCLUSION: Clinical improvement after manual therapy is accompanied by restoration of CPM and TSP responses to normal levels in NSCNP patients. The existence of only minor associations between changes in central pain processing and clinical outcome suggests multiple mechanisms of action of manual therapy in NSCNP.
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Dolor Crónico , Manipulaciones Musculoesqueléticas , Dolor de Cuello , Dimensión del Dolor , Umbral del Dolor , Humanos , Femenino , Dolor de Cuello/terapia , Dolor de Cuello/fisiopatología , Persona de Mediana Edad , Masculino , Dolor Crónico/terapia , Dolor Crónico/fisiopatología , Adulto , Manipulaciones Musculoesqueléticas/métodos , Resultado del Tratamiento , Estudios de CohortesRESUMEN
OBJECTIVE: Evidence suggests altered pronociceptive and antinociceptive mechanisms in many chronic pain conditions. Knowledge about these mechanisms in nonspecific chronic neck pain (NSNP) would improve understanding of the causes and the design of more effective treatments. Pressure pain threshold (PPT) is often used to assess presence of altered nociceptive processing in NSNP; however, its usefulness to detect this is yet to be established. The purpose of this study was to determine the functional status of temporal summation of second pain (TSSP) and conditioned pain modulation (CPM) in NSNP and to characterize the association of both measures with PPT and clinical features of NSNP. METHODS: Thirty-two participants with NSNP (mean [SD] age = 44 [11] years; 27 female) and 32 age- and sex-matched healthy controls were recruited. TSSP was assessed using an electrical stimulus at the dorsum of the hand, and CPM was evaluated with the Cold Pressor Test. PPT was assessed bilaterally at the neck and tibialis anterior muscles. RESULTS: Participants with NSNP showed greater TSPP (mean difference = 0.23; 95% CI = 0.46-0.01; Cohen d = 0.51) and lower CPM (mean difference = 19.44; 95% CI = 10.42-28.46; Cohen d = 1.09). Pooled data from all participants showed lower PPTs at the neck than the tibialis anterior. However, PPT measures did not differ between groups at either location. PPT measures were not correlated with CPM and TSP. CONCLUSION: NSNP is associated with enhanced pronociceptive and impaired antinociceptive mechanisms, which may explain long-lasting pain and failure of some treatments to resolve symptoms. However, due to the observational nature of this study, a clear cause-effect relationship cannot be established. Normal PPT values in the clinic should not be interpreted as absence of altered nociceptive processing. IMPACT: This study fills in some gaps in knowledge. Changes in central nociceptive processing may explain persistent and recurrent symptoms in NSNP and failure of treatments to obtain long-lasting relief. Further research is required to ascertain if TSSP and CPM assessment in the clinic may help predict physical therapy treatment outcome. Whether symptomatic relief with physical therapy is mediated by an improvement in TSSP and CPM should also be explored. PPTs were unaltered in participants with NSNP despite evidence of impairment in the central pain modulatory systems. Normal PPTs should not be interpreted as evidence of unaltered central pain-related processing.
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Sensibilización del Sistema Nervioso Central/fisiología , Dolor Crónico/fisiopatología , Dolor de Cuello/fisiopatología , Umbral del Dolor/fisiología , Adulto , Estudios de Casos y Controles , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del DolorRESUMEN
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Humanos , Masculino , Adolescente , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/cirugía , Aloinjertos/diagnóstico por imagen , Arteria Pulmonar/cirugía , Prótesis Valvulares Cardíacas , Arteria Pulmonar/diagnóstico por imagen , Aloinjertos/cirugía , Función VentricularRESUMEN
Stilbene-derived optical brighteners can markedly enhance the insecticidal activity of certain baculoviruses. We evaluated the influence of an optical brightener on the rate at which Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) developed resistance to nucleopolyhedrovirus (SfMNPV). Two laboratory colonies of S. frugiperda were inoculated with an LC50 of SfMNPV, in the absence or presence of the optical brightener Tinopal LPW (0.1%), over a period of two and 11 generations, in the first and second experiment, respectively. Compared with the initial susceptibility of the insect colony, resistance ratios of 11- and 12-fold were observed after two generations of treatment with SfMNPV + Tinopal LPW and SfMNPV alone. Similar, but variable degrees of resistance were observed in the long-term experiment with resistance ratios of 8- to 35-fold after seven to 11 generations. The presence of Tinopal LPW alone, or in mixtures with SfMNPV, did not cause any systematic change in insect resistance in either experiment. At the end of the long-term experiment, debilitating effects on pupal weight, adult fecundity, and longevity were observed in the insects exposed to Tinopal LPW alone or in mixtures with SfMNPV, but the pattern of such effects among treatments differed in each generation. We conclude that optical brighteners are unlikely to affect the rate of development of resistance to nucleopolyhedroviruses applied as biological insecticides.
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Nucleopoliedrovirus/fisiología , Control Biológico de Vectores/métodos , Spodoptera/virología , Estilbenos/farmacología , Animales , Selección Genética , Spodoptera/genéticaRESUMEN
OBJECTIVE: To report a clinically severe interaction between ritonavir (RTV) and acenocoumarol resulting in a decrease in the anticoagulant effect severe enough to eventually preclude RTV administration. CASE SUMMARY: An asymptomatic, HIV-infected, 46-year-old man with mitraortic prosthetic valves receiving acenocoumarol therapy started stavudine, lamivudine, and RTV 600 mg twice daily. His international normalized ratio (INR) decreased dramatically (the opposite of what should be expected). Although the acenocoumarol dose was progressively increased to 3 times the original dose, it was impossible to achieve the previous INR and RTV was withdrawn. DISCUSSION: RTV is an inducer of the hepatic isoenzymes CYP1A2, CYP1A4, and CYP2C9/19 and leads to extensive metabolism of acenocoumarol that cannot be balanced by dose increases. This effect is the opposite of what was expected to occur, considering that RTV is also a strong inhibitor of most hepatic isoenzymes. CONCLUSIONS: RTV severely decreases the anticoagulant effect of acenocoumarol. It must be added to the list of drugs that affect the action of oral anticoagulants, and it probably should be avoided in patients receiving acenocoumarol.