Differential roles of neurokinin 1 and neurokinin 2 receptors in the development and maintenance of heat hyperalgesia induced by acute inflammation

1. Following induction of acute inflammation by intraarticular injection of kaolin and carrageenan into the knee joint in rats, there was a significant decrease in the withdrawal latency to radiant heat applied to the paw (i.e. heat hyperalgesia), an increased joint circumference and increased joint temperature.
2. A neurokinin₁ (NK₁) receptor antagonist (CP-99,994, 10 mM) had no effect on the paw withdrawal latency when it was administered spinally through a microdialysis fibre before the induction of inflammation. Pretreatment with a NK₂ receptor antagonist (SR48968, 1 mM) administered spinally through the microdialysis fibre prevented the heat hyperalgesia from developing in the early stages of the inflammation.
3. Post-treatment through the microdialysis fibre with the NK₁ receptor antagonist (0.0110 mM) was effective in reversing the heat hyperalgesia. In contrast, post-treatment spinally with the NK₂ receptor antagonist (0.011 mM) had no effect on the heat hyperalgesia. The inactive stereoisomers of the NK₁ receptor antagonist, CP100,263, or the NK₂ receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia.
4. Pretreatment systemically with the NK₁ receptor antagonist (30 mg kg⁻¹) had no effect on the heat hyperalgesia or pain-related behaviour ratings where 0 is none and 5 is non weight bearing and complete avoidance of limb contact. Pretreatment with a NK₂ receptor antagonist (10 mg kg⁻¹) systemically prevented the heat hyperalgesia and pain-related behaviour ratings from developing in the early stages of the inflammation. The inactive stereoisomers of NK₁ receptor antagonist, CP100,263, or the NK₂ receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia.
5. Post-treatment systemically with either the NK₁ (0.130 mg kg⁻¹) or the NK₂ (0.110 mg kg⁻¹) receptor antagonist resulted in a dose-dependent reversal of the heat hyperalgesia. Pain-related behaviour ratings were reduced by post-treatment only with the NK₁ receptor antagonist. The inactive stereoisomers of the NK₁ receptor antagonist, CP100,263, or the NK₂ receptor antagonist, SR48965, administered at the same doses, had no effect on the behavioural responses.
6. Direct pretreatment of the knee joint with either the NK₁ (30 mg) or the NK₂ (10 mg) receptor antagonist prevented the heat hyperalgesia from developing without affecting joint swelling. The inactive stereoisomers of the NK₁ receptor antagonist, CP100,263, or the NK₂ receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia.
7. There appears to be a differential role for the spinal tachykinin receptors in the development and maintenance of the heat hyperalgesia associated with acute joint inflammation. The NK₂ receptors appear to be activated early in the development of the heat hyperalgesia and NK₁ receptors are involved in the maintenance of the heat hyperalgesia.
8. Peripherally, both NK₁ and NK₂ receptors are involved in the development of heat hyperalgesia and pain-related behaviour ratings induced by acute inflammation.

     

类风湿性关节炎患者血清IL-6、TNF水平变化及其意义探讨

采用细胞生物学方法测定类风湿性关节炎（ Ｒ Ａ）１４ 例血清 Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 水平,均显著高于正常对照组（ Ｐ＜ ０ ．００１） 。相关分析显示 Ｉ Ｌ－ ６ 与 Ｔ Ｎ Ｆ 水平变化呈正相关（ Ｐ＜ ０ ．０１） , Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 与血沉亦呈正相关（ Ｐ＜０ ．０５） 。认为, Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 参与 Ｒ Ａ 的发病,两者在致病中有协同相同;其水平变化与 Ｒ Ａ 的活动性及血沉相关。     

Clinico-immunological profile in juvenile rheumatoid arthritis—an Indian experience

From a Pediatric Rheumatology Clinic 361 children diagnosed as juvenile rheumatoid arthritis (JRA) according to American Rheumatism Association-JRA criteria were studied retrospectively for their clinico-immunological profile. The mean age of onset in systemic, pauciarticular and polyarticular onset, JRA subtypes were 5.2, 6.8 and 7.2 years respectively. There was male preponderance in systemic and pauciarticular JRA. In seropositive polyarticular JRA, girls outnumbered boys. The frequency of occurence of systemic, pauciarticular and polyarticular disease was 87 (24%), 108 (30%) and 166 (46%) respectively. The systemic onset disease was dominated by extra-articular manifestations in terms of fever (100%), rash (57%), hepatomegaly (51%) and lymphadenopathy (25%). The pauci- and polyarticular illnesses were commonly dominated by joint involvement, morning stiffness, and in few patients, by extra-articular manifestations also. The joints were involved symmetrically. Most commonly involved joints in order of decreasing frequency were knee, ankle, wrist and elbow in all the subtypes. Anemia and leucocytosis were observed in majority with higher frequency in systemic onset JRA. The rheumatoid factor (RF) was present in 15% of polyarticular JRA. RF was also present in 7 and 9% of patients with pauciarticular and systemic subtypes respectively. The antinuclear antibody was positive in only 3 out of 66 patients in whom the test was carried out. The demographic profile and trends in clinical features were similar to the studies reported on caucasian population with difference in the actual frequency of various clinical features.     

Coping with rheumatoid arthritis. How can specialist nurses influence it and promote better outcomes?

• ? Psychological stressors are said to be an important influence on the outcome of chronic illnesses such as rheumatoid arthritis (Engel, 1977).
• ? Helping patients to cope with stressors is identified as a central concept in the delivery of nursing care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology nurses may be key players in the process of coping with rheumatoid arthritis.
• ? But in order for rheumatology nurses to be effective players in this process, they need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an overall behaviour pattern linked to a better outcome. Literature showing the link between different coping behaviours and outcome is examined, and cognitive restructuring is emphasized as one method nurses could use.
• ? Having identified coping behaviour which is optimal in terms of future outcome, further study of different forms of coping-based educational intervention is suggested, to reveal how such patterns of behaviour can be taught by nurses in the most effective way

     

Plasma protein binding of prednisolone in normal volunteers and arthritic patients

Summary The plasma binding of prednisolone was studied in twenty normal volunteers and twenty rheumatoid arthritis patients. An in vitro assessment of the binding following the addition of prednisolone, prednisone, and hydrocortisone to the plasmas obtained from the subjects showed significant differences in the percentage of prednisolone bound. However, the differences observed were regarded as clinically insignificant. The plasma protein binding was determined by an in vitro equilibrium dialysis of the individual plasma samples at 37° C. Prednisolone levels on both sides of the dialysis membrane were determined using radioactivity and HPLC analytical methodologies. The percentages of prednisolone bound calculated from the analytical results of either the radiochemical or HPLC method were not significantly different. The change in the percentage of prednisolone bound to plasma proteins was studied as a function of the total prednisolone plasma concentration in a normal volunteer and in a systemic lupus erythematosis patient. As a result of prednisolone binding to both transcortin and albumin, the binding of prednisolone changes as a function of prednisolone concentration. The binding data were fitted using nonlinear least squares regression, and the affinity constants for the binding of prednisolone to transcortin and albumin were estimated.     

Reiter's syndrome following intravesical BCG immunotherapy

A 71 year old woman developed conjunctivitis, asymmetrical oligoarthritis, and cystitis (Reiter's syndrome) secondary to intravesical BCG treatment for transitional cell carcinoma of the bladder. She received oral prednisolone, izoniazid, and pyridoxine and made a full recovery. Increasing use of BCG as immunotherapy will lead to an increase in the incidence of BCG associated reactive arthritis. Prompt recognition and early diagnosis will facilitate treatment and recovery.     

正清风痛宁缓释片治疗类风湿关节炎60例疗效观察

2003年1月～2005年8月,我们使用正清风痛宁缓释片治疗类风湿关节炎(rheumatoidarthritis,RA)60例,并以甲氨蝶呤作为对照药物,现将结果报道如下。1资料与方法1.1一般资料2003年1月～2005年8月,共收集我院门诊诊断为RA的患者120例,符合美国风湿病协会1987年RA分类标准[1],且至少3     

The frequency and characteristics of ultrasonographic ankle joint involvement in systemic lupus erythematosus: A prospective cross-sectional single-center study

The involvement of ankles in systemic lupus erythematosus (SLE) has not been widely studied. The aim of our prospective study was to determine the characteristics of the ankle joint and tendon involvement in SLE using ultrasound (US) as an imaging modality. Sixty consecutive patients with SLE underwent a detailed clinical evaluation and US examination. Gray-scale and power Doppler US of the bilateral tibiotalar (TT) joints, subtalar (ST) joints, and ankle tendons were performed using a multiplanar scanning technique. Joint effusion, synovitis, tenosynovitis, enthesitis, and vascularization were assessed according to the OMERACT recommendations. The Total Ankle Ultrasound Score (TAUSS) was calculated as the sum of the grades of joint effusion and synovial hypertrophy for both TT and ST joints bilaterally (ranging from 0–24) and power Doppler activity was assessed separately. Finally, US findings were correlated with physical evaluation, laboratory parameters, and SLE activity scores. US ankle joint involvement was present in 32/60 (53.3%) patients. TT joints were affected in 26 (43.3%) and ST joints in 16 (26.7%) patients. Thirteen (21.7%) patients had US tendons and/or enthesal involvement. TT joint effusion was the most frequent finding, present in 55/240 (22.9%) examined joints, followed by synovial hypertrophy detected in 18/240 (7.5%) joints. The median (interquartile range; range) TAUSS of the US-affected joints was 1 (0–2; range 1–10). There were no significant correlations between US findings and inflammatory parameters or serological parameters of disease activity, but we found a weak positive correlation between TAUSS and the European Consensus Lupus Activity Measurement (r = 0.281, P = .029). This study revealed a high prevalence of pathological US ankle changes in patients with SLE and a positive correlation between ankle US involvement and disease activity score (European Consensus Lupus Activity Measurement).