Steinar Hunskaar

The formalin test: an evaluation of the method

&NA; The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C‐fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C‐fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception.

The formalin test in mice: dissociation between inflammatory and non-inflammatory pain

&NA; The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non‐steroid anti‐inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti‐inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non‐inflammatory pain.

A community-based epidemiological survey of female urinary incontinence: The Norwegian EPINCONT Study

OBJECTIVES The aim was to assess the prevalence of any urinary leakage in an unselected female population in Norway, and to estimate the prevalence of significant incontinence. METHODS The EPINCONT Study is part of a large survey (HUNT 2) performed in a county in Norway during 1995-97. Everyone aged 20 years or more was invited. 27,936 (80%) of 34,755 community-dwelling women answered a questionnaire. A validated severity index was used to assess severity. RESULTS Twenty-five percent of the participating women had urinary leakage. Nearly 7% had significant incontinence, defined as moderate or severe incontinence that was experienced as bothersome. The prevalence of incontinence increased with increasing age. Half of the incontinence was of stress type, 11% had urge and 36% mixed incontinence. CONCLUSIONS Urinary leakage is highly prevalent. Seven percent have significant incontinence and should be regarded as potential patients.

FORMALIN TEST IN MICE, A USEFUL TECHNIQUE FOR EVALUATING MILD ANALGESICS

A modification of the formalin test appropriate for testing of mice is described. Formalin 1 or 5% was injected into the dorsal surface of a hindpaw, and the time the animal spent licking the paw was recorded. On the basis of the response pattern, two distinct periods of intensive licking activity were identified; an early (0-5 min after injection) and a late response (20-30 min after injection). The following analgesics were investigated (dose range): acetylsalicylic acid (100-400 mg/kg), paracetamol (100-400 mg/kg) and morphine (0.6-10 mg/kg). Acetylsalicylic acid (200-400 mg/kg early response, 300-400 mg/kg late response), paracetamol (200-400 mg/kg early response, 300-400 mg/kg late response) and morphine (2.5-10 mg/kg) inhibited the responses in a dose-dependent manner. The results indicate that the test is useful for evaluating mild analgesics. It may have advantages over some of the tests that are commonly used for testing analgesics.

The prevalence of urinary incontinence in women in four European countries

To determine the prevalence, type and treatment behaviour of women with urinary incontinence in four European countries.

The Quality of Life in Women with Urinary Incontinence as Measured by the Sickness Impact Profile

The objectives of this paper were to assess the quality of life of community‐living women with urinary incontinence according to age, symptom group, amount of leakage, and duration, by use of the Sickness Impact Profile (SIP). Thirty‐six women aged between 40 and 60 years and 40 women aged 70 years or more were randomly selected from the clients attending an incontinence clinic and interviewed using the SIP questionnaire. Urge and stress incontinence subgroups were defined by means of a symptom questionnaire. Total, psychosocial, and physical dysfunctions were moderate (8%, 7%, and 8% respectively) in general, but major differences were found when age and symptom groups were analysed. Urge symptoms were associated with more impairment than symptoms of stress incontinence. The elderly women with symptoms of stress incontinence were relatively little affected, while their younger counterparts were severely affected, especially in the categories of emotional behavior and recreation and pastimes. We conclude that urinary incontinence in women adversely affects quality of life to a significant degree; the extent depends on the nature of incontinence and the age of the person.

Are smoking and other lifestyle factors associated with female urinary incontinence? The Norwegian EPINCONT Study

Objective To examine whether modifiable lifestyle factors such as smoking, obesity, physical activity and intake of alcohol or caffeinated drinks were associated with urinary incontinence in women.

Age- and Type-Dependent Effects of Parity on Urinary Incontinence: The Norwegian EPINCONT Study

OBJECTIVE To investigate the association between parity and urinary incontinence, including subtypes and severity of incontinence, in an unselected sample, with special emphasis on age as a confounder or effect modifier. METHODS This was a cross‐sectional study (response rate 80%) with 27,900 participating women. Data on parity and urinary leakage, type, frequency, amount, and impact of incontinence were recorded by means of a questionnaire. A validated severity index was used. Relative risks (RR) with nulliparous women as reference were used as an effect measure. RESULTS Incontinence was reported by 25% of participants. Prevalences among nulliparous women ranged from 8% to 32%, increasing with age. Parity was associated with incontinence, and the first delivery was the most significant. The association was strongest in the age group 20–34 years with RR 2.2 (95% confidence interval [CI] 1.8, 2.6) for primiparous women and 3.3 (2.4, 4.4) for grand multiparous women. A weaker association was found in the age group 35–64 years (RRs between 1.4 and 2.0), whereas no association was found among women over 65 years. For stress incontinence in the age group 20–34 years, the RR was 2.7 (2.0, 3.5) for primiparous women and 4.0 (2.5, 6.4) for grand multiparous women. There was an association with parity also for mixed incontinence, but not for urge incontinence. Severity was not clinically significantly associated with parity. CONCLUSION Parity is an important risk factor for female urinary incontinence in fertile and peri‐ and early postmenopausal ages. Only stress and mixed types of incontinence are associated with parity. All effects of parity seem to disappear in older age.

Epidemiology and natural history of urinary incontinence in women

Understanding the epidemiology (distribution and determinants) of urinary incontinence (UI), as well as its natural history is a very important issue. In this article, we discuss prevalence, incidence, natural history, and the variations that may be related to race and ethnicity. We focus on epidemiologic population comprising community-dwelling women who are not institutionalized. Our review clearly shows that there is a lack of advanced epidemiologic analyses. Variables that better characterize UI include frequency measure, quantity of urine loss, duration, type, and severity. These factors should be incorporated into basic study design so that more advanced and informative analyses may be conducted.

A Systematic Review of Overweight and Obesity as Risk Factors and Targets for Clinical Intervention for Urinary Incontinence in Women

To review the epidemiological literature of urinary incontinence with respect to overweight and obesity as a risk factor, and how the findings eventually fulfill general criteria for being a causal factor for the condition. Likewise to review all interventional studies assessing the effect of weight reduction on incontinence.