"Clinical mastitis is the most common disease of dairy cows in many well-managed dairies throughout the world." (J234.8.w1)

Mastitis is an important production disease in dairy herds in the UK, with significant costs to the farmer associated with loss of milk yield, discarded milk during treatment with drugs, costs of drugs and, for severe cases, veterinary treatment, and an increased risk of culling. (J35.154.w1, J303.12.w2)

• A three-year survey 1980-1983 determined an annual incidence varying from 54.6 cases per 100 cows per year in 1980 to a low of 41.2 cases per 100 cows in 1982. It was found that incidence increased with the age of the cow and declined with increasing herd size. The culling rate due solely to mastitis was 3% while in a further 3% of cases mastitis was a contributory factor in the decision to cull (overall culling rate in these herds 19%). (J3.118.w5)
• A survey 1994-1995 in dairy herds, average size 132 cows, in England found a mean annual incidence of 39.9 cases per 100 cows or 43.4 quarter cases per 100 cows, with 25.9% of cows affected (1.6 quarter-cases per affected cow). There was no affect of herd size on incidence of mastitis. (J3.143.w7)

While subclinical mastitis due to Streptococcus agalactiae and Staphylococcus spp. may be reduced by effective control programmes, such programmes do not exist for control of acute and peracute mastitis caused by environmental pathogens such as coliform bacteria. (J234.8.w1, J234.19.w1)

In sheep:

• Mastitis in ewes is seen in most flocks in the UK with an annual incidence which may vary from 1% to 15% per flock; it is generally more common in lowland flocks than in hill flocks. The main organisms involved are Staphylococcus aureus and/or Mannheimia (Pasteurella) haemolytica. (J15.23.w1)

• --

• Mastitis in mammals is very painful. (B344.55.w55)
  • Affected tissues are extremely sensitive to touch. (J310.64.w1; B344.55.w55)
• Mastitis is a common condition likely to be associated with pain in cattle. (J303.12.w1)
• It is generally accepted that severe mastitis is extremely painful, although the degree of pain associated with milder forms of mastitis is less clear. (J303.7.w1, P55.1998.w1)
  • Pain in the affected quarter is one of the signs (others being heat, redness and swelling) which has been used to distinguish mild mastitis (presence of altered milk only) from moderate mastitis. (J3.148.w8)
  • Lack of consensus regarding the degree of pain in milder mastitis cases may be due to the difficulties in perceiving and measuring pain in stoical ruminant species. (J303.7.w1)
  • Pain is one of the signs of mastitis in the udder, which may also be hot, swollen and hard. (B353.w3)
• Pain in mastitis is caused by inflammation of the udder, increased intramammary pressure, and increased external pressure (e.g. from an adjacent limb on a swollen udder). (P55.2003.w1)
• Production of bradykinin, a potent inducer of pain and oedema, is considerably raised in the mastitic udder. (J310.64.w1)
• Signs of pain and irritation associated with mastitis include kicking at the udder. (J3.124.w3)
• Pain in mastitis may give rise to allodynia, with even gentle touching of the udder being resented due to pain. (B322.4.w4)
• Studies of the pain threshold of cows with and without mastitis have found that the pain threshold, measured using a mechanical stimulus, was lowered even in mild mastitis, strongly suggesting an increased sensitivity to pain (hyperalgesia) and, therefore indicating that pain is present even in mild mastitis cases. (P55.1998.w1, P55.2003.w2)
  • In a study of more than 100 cows (61 mild and 56 moderate cases) with mastitis, compared with 45 normal cows, the mechanical pain threshold was significantly lower (P<0.01) in the cows with mastitis than in the normal cows. (P55.2003.w2)
• A survey of veterinarians in cattle practice attending a BCVA meeting found that on a scale of 0 (no pain) to 10 (high pain), mastitis was given a mean score of 4.9, median score 5 and inter-quartile range 4 to 6 but with a wide range of scores, with 5.1% of respondents giving a score of 1 and 11.4% a score of 7 to 9. The authors considered that the range of pain scores given at least partly was a reflection of the variation in mastitis. (J303.10.w1)
• Treatment of cows with mild mastitis with the NSAID flunixin meglumine reduced sensitivity to pain. (J303.7.w1, P55.1998.w1)
• Even cows with mild mastitis have exhibited a decreased pain threshold (hyperalgesia). (J303.12.w1)
• The degree of pain in mastitis is generally assessed subjectively, based on the general demeanour of the affected animal, responses to palpation of a swollen quarter of the udder, reluctance of the animal to walk and abduction of the hind leg away from the affected quarter. (P55.2003.w1)
• Heart rates, respiratory rates and rectal temperatures [all of which may be raised in individuals experiencing pain] of cows with moderate mastitis were found to be significantly higher (P<0.001) than in normal cows or those with only mild mastitis. (P55.2003.w2)
• In a grading system of Grade 1 to Grade 3 for clinical mastitis, pain in the affected quarter is noted as one of the clinical signs of mastitis of Grade 2 or 3. (B347.w1)

In sheep and goats:

• It is recognised that both acute and chronic mastitis in ewes is painful. (B217.11.w11)
• The affected side of the udder is painful, hot, red and swollen. (B207.15.w15, B217.11.w11, J15.23.w1)
  • In acute gangrenous mastitis the affected gland quickly becomes cold and purple. (B207.15.w15, J15.23.w1)
• Sheep with acute mastitis walk stiffly and appear lame or the affected side. (B346.w4, J15.23.w1) or may drag the leg of the affected side. (J15.23.w1, B359.7.w7)
• In milking ewes and dairy goats acute forms of mastitis may occur similar to those in cattle. (B207.15.w15)

• Assessment of Pain in Ruminants

• Pain is a welfare problem for the affected animal. (J303.7.w1)
• Pain results in reduced appetite, reduced willingness to move to sites where food is available and reduced milk yields: these all have deleterious economic effects for the farmer. (J303.7.w1, P55.1998.w1)
• Cows with mastitis, even mild or moderate mastitis, have increased sensitivity to pain. (J303.7.w1, P55.1998.w1)

Further information on the negative effects of pain is provided in: Reasons for Pain Relief - Disadvantages of pain to the animal

• Reasons for Pain Relief - Disadvantages of pain to the animal

• Treating pain associated with mastitis should be beneficial both to the cow (welfare) and to the farmer (economic benefits). (J303.7.w1, P55.1998.w1)
  • Economic benefits should result from a reduction in the negative effects of pain (see above). (J303.7.w1, P55.1998.w1)
  • "There is a growing realisation that effective treatment [of mastitis] may also involve medication or physiological applications to ameliorate pain, inflammation, dehydration etc." (P55.1998.w2)

• Reasons for Pain Relief

Prevention of mastitis:

• Prevention of mastitis is more effective and economical than its treatment, and measures to prevent mastitis should be practiced. (J234.19.w1)
• In sheep: 
  • Prevention is important. Correct nutrition to ensure adequate body condition and thus sufficient milk production to feed the lambs in early lactation is important to prevent all types of mastitis. Improvement of management may remove factors predisposing to acute gangrenous mastitis. Use of long-acting intramammary preparations designed for cattle may be appropriate in some circumstances. (J15.23.w1)
  • Appropriate treatment of teat lesions (seen at the base of the teat) associated with Staphylococcus aureus infection (also with orf) may prevent development of mastitis. Appropriate treatment includes use of a NSAID (particularly important) together with a parenteral broad-spectrum antibiotic, application of an antiseptic cream to the teats and periodic restraint of the ewe (several times daily) to ensure suckling by the lambs thus preventing build-up of milk in the udder. (J15.23.w1)

Treatment of mastitis:

• Treatment of severe clinical mastitis is necessary "if only to relieve the cow of systemic signs. Supportive care is indicated in most cases and "in the case of coliform mastitis, may be the most beneficial component of the therapeutic regime." Antibacterial therapy is also an integral part of the treatment of severe mastitis. (J234.19.w1)
• Treatment of mastitis may include intramammary and/or systemic antibiotics as well as supportive treatment such as frequent stripping of milk from the affected quarter, corticosteroids, NSAIDs, and, in individuals showing dehydration and acidosis, fluid therapy. (J35.145.w1)
• Appropriate antibiotic treatment may be important in preventing progression of mastitis to a more severe clinical disease [and therefore presumably to a more painful stage of disease]. (J4.213.w1)
• In sheep both parenteral administration of a broad-spectrum antibiotic and infusion of a cattle intramammary preparation into the affected gland is suggested for acute cases detected very early. (J15.23.w1)

Nursing care:

• Ensuring that the affected animal has a dry, comfortable bed with good non-slip flooring, and is provided with food and water frequently, is important. (B347.w1)

Provision of analgesics:

NOTE: licensing of drugs for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, vary between countries and change with time. Withdrawal times may also vary between preparations and depending on route of administration. Current information (e.g. a current manufacturer's datasheet) for the drug preparation to be used should always be consulted to prior to use. In the UK the prescription cascade must be followed.

NSAIDs:

• NSAIDs are commonly used by dairy practitioners in the treatment of acute mastitis in cows. (J234.19.w1, B351.34.w16)
• The analgesic, anti-inflammatory, anti-endotoxic and anti-pyretic effects of NSAIDs are all beneficial to a cow with mastitis. (P55.2003.w1)
• Use of NSAIDs in supportive treatment of mastitis provides symptomatic relief and improves the systemic well-being of the cow (J234.19.w1, B353.w3) as well as assisting in minimising parenchymal damage. (B353.w3)
• Provision of an NSAID by intravenous injection often produces a marked improvement in demeanour in cows with toxic mastitis therefore "their use for pain relief is justifiable and logical." (J15.20.w4)
  • Give for 24-72 hours starting with a dose at the upper limit of the recommended range for whichever NSAID is chosen. (J15.20.w4)
  • Which NSAID should be given must be decided by each individual practitioner based on clinical responses to therapy of patients under their care; "there is no convincing evidence that any one product gives greater success than another."  (J15.20.w4)
• Three NSAIDs are licensed for use to treat mastitis in cattle in the UK:
  • Flunixin meglumine for up to five consecutive days, 1000 mg intravenously or intramuscularly as a first dose, then 500 mg every 12 hours. (J303.7.w1, P55.2003.w1)
  • Ketoprofen for up to three consecutive days (J303.7.w1, P55.2003.w1); 3 mg/kg by intravenous or intramuscular injection daily for up to three days. (P55.2003.w1)
  • Tolfenamic acid. (J303.12.w1, B266); single intravenous injection of 4 mg/kg bodyweight. (B266)
• Phenylbutazone has been widely used for the treatment of acute mastitis however its use in food animals is strongly discouraged in the USA by FARAD and the FDA-CVM), with a tolerance level for the drug in any animal product of zero; the withdrawal period is long and any concentration of the drug detected in animal products in the USA is illegal. (J234.19.w1) Effective 29th May 2003, phenylbutazone was added to the list of drugs prohibited for use in female dairy cattle aged 20 months or older. (W509.June04.w1) This drug has been withdrawn from use for food-producing animals in the UK. (J303.7.w1)
• Aspirin [which is not licensed for use in cattle in the UK] has been used to alleviate pain and as an antipyretic in acute mastitis, at 100 mg/kg orally every twelve hours. (J35.145.w1)
  • Caution is recommended in the use of oral aspirin in cases of acute coliform mastitis since many cows with this condition develop severe atony of the rumen. A milk and meat withdrawal time of 24 hours is recommended by FARAD in the USA to reduce the risk of Reye's syndrome in children. (J234.19.w1)
  • 30 g orally as a drench twice daily. This is no longer licensed for use in cattle in the UK. (B347.w1)
• Flunixin meglumine is currently [2003 data] the only NSAID labelled for use in cattle in the USA (labeled for use in beef and non-lactating dairy cattle with bovine respiratory disease). It should reduce clinical signs including udder pain as well as fever, depression and heart and respiratory rate changes. If this drug is used as recommended for use in beef and non-lactating dairy cattle then milk and meat withdrawal times of 72 hours and four days respectively are suggested by FARAD. (J234.19.w1)
• Some experimental data on the use of NSAIDs in mastitis in cattle:
  • Experimentally, repeated administration of flunixin meglumine at 1.1 mg/kg (initially intravenously, thereafter intramuscularly at eight-hour intervals) reduced pain as well as oedema, quarter size and quarter temperature in cows with endotoxin-induced mastitis. (J13.47.w1)
  • In clinical cases of mastitis, ketoprofen given at 2 g of 10% solution per cow intramuscularly once daily resulted in a higher rate of recovery than non-blind contemporary controls (84.7% versus 83.7%) and a significantly higher rate of recovery compared with blind placebo controls (92.3% versus 70.7%, P<0.01). The effect of the NSAID on pain in the cows was not specifically mentioned. (J21.56.w2)
  • In cows with experimentally induced Escherichia coli endotoxin mastitis, treatment with a single dose of carprofen (0.7 mg/kg intravenously) significantly reduced clinical signs of mastitis including swelling of the quarter (P<0.01), rectal temperature (P<0.001), heart rate (P<0.01) and general depression (P<0.01). (J289.14.w2)
  • In cows with experimentally induced Escherichia coli endotoxin mastitis, the NSAID ibuprofen, at 25 mg/kg bodyweight by slow intravenous injection, significantly reduced rectal temperature, heart rate and respiratory rate although size and firmness of the inoculated quarter were not affected. (J13.54.w3)
  • In cows with mild mastitis, but not in cows with moderately severe mastitis, a single injection of flunixin meglumine (Finadyne, Schering-Plough Animal Health) at 2.2 mg/kg intravenously, alongside antibiotic treatment, reduced the increased sensitivity to pain seen in the mastitic cows. (J303.7.w1, P55.1998.w1)
  • In cows with experimentally induced Escherichia coli mastitis, intravenous injection of flunixin meglumine (1.1 mg/kg intravenously or 2.2 mg/kg intramuscularly) or with flurbiprofen (2 mg/kg intravenously) decreased the amount of kicking at the udder as well as decreasing the febrile response and preventing the decrease in ruminal contraction frequency and amplitude seen in untreated cows. (J3.124.w3)
  • In cows with endotoxin-induced mastitis, injection with flunixin meglumine at 2.2 mg/kg intravenously after the onset of clinical signs of mastitis (rectal temperature > 40°C and presence of mammary swelling) was found to increase rumen motility, decrease rectal temperature and reduce mean heart rate; it did not ameliorate either swelling of the mammary gland or loss of milk production. A specific effect on pain was not mentioned. (J13.65.w1)
  • In cows with acute toxic mastitis, 1 g flunixin meglumine intravenously or 4 g phenylbutazone intravenously, given once, together with intramammary antibiotic treatment, did not produce any difference in rectal temperature, heart rate, respiratory rate, appetite or rumen motility measured 24 hours later, nor affect loss of milk in the cows with mastitis. (J13.56.w)
• In sheep: 
  • Provision of analgesia is an important consideration in mastitis in sheep. (B217.11.w11, J15.23.w1)
  • Administration of a NSAID such as flunixin meglumine is indicated as part of treatment of mastitis in sheep. (B346.w4, B359.7.w7, J15.23.w1)
    • In sheep with acute mastitis, administration of flunixin meglumine at 1.82-2.33 mg/kg (100 mg per ewe) on two occasions, 24 hours apart, resulted in a significantly faster resolution of clinical signs (mean rectal temperature and mean total clinical reaction score, rate of reduction for each of these significantly greater (P<0.01)), notable by the second day of treatment. Bacteriological cure rates were not affected. (J289.23.w1)

Opiates:

• Opiates are not licensed for use in any food-producing species in the UK. (J303.7.w1, P55.1998.w1)
• Buprenorphine, 1.2 mg/kg by intramuscular injection at 24-hour intervals in cows with mastitis, "has been found by the author to be followed by an improvement in the cow's demeanour and appetite." (J35.145.w1)

Corticosteroids:

• Corticosteroids are not ideal for use in cows with mastitis. They may have immunosuppressive effects and they should not be given to pregnant animals. (J303.7.w1, P55.1998.w1)
• It has been suggested that a single dose of glucocorticoids such as dexamethasone may be appropriate for use early in the course of severe cases of gram-negative mastitis for their anti-inflammatory effects. (J234.19.w1)
• These may be useful early in mastitis, but are "of little value" in established infections. (P55.2003.w1)
• Intramammary preparations containing corticosteroids [in addition to antibiotics] may be preferred by some farmers as they can produce a rapid reduction in inflammation of the udder. (P55.2003.w1)

Alpha-2 agonists:

• Xylazine is not ideal for use in cows with mastitis; it has a prolonged sedative effect. (J303.7.w1, P55.1998.w1)

Euthanasia:

• This may be the most appropriate form of pain relief in cases with a hopeless prognosis, such as with gangrenous mastitis, in both cattle and sheep. (P55.2003.w1, J15.23.w1)

• Alleviation of Pain Associated with Painful Conditions in Ruminants
• Groups of Analgesic Drugs
• Routes of Drug Administration in Ruminants
• Understanding Pharmacokinetics for Pain Management in Ruminants

• Attitudes towards pain in animals;
• Tradition;
• Failure to recognise pain;
• Failure to recognise the importance of the adverse effects of pain;
• Concern about removing possible protective effects of pain [this concern is generally excessive];
• Concern that providing pain relief may itself stress the animal and have a negative impact on it;
• Concern that treating pain may interfere with diagnosis;
• Lack of information about analgesics;
• Concern about toxicity and side-effects of analgesics;
• Concerns about the safety and legislative controls associated with some analgesics such as opiates;
• Economic and practical considerations.

Specific published reasons for failure to provide pain relief in mastitis are indicated below.

• Tradition:
  • Many texts describing treatment of mastitis either do not address pain relief as part of that treatment, or indicate that pain relief is of minor importance compared to other components of treatment, or mention use only for severe cases of mastitis. (V.w5)
• Failure to recognise pain:
  • Pain associated with mastitis may not be recognised. (J303.7.w1, P55.1998.w1, P55.2003.w1)
  • Concerns regarding economic effects of discarded milk, effects on normal milking routines, etc., may be more prominent than concerns about pain associated with the condition. (P55.2003.w1)
• Economic and practical considerations:
  • "In dairy cows mastitis is almost certainly painful but the use of analgesics may be considered too expensive." (P61.62.w1)
  • NSAIDs are often used only in severe cases of mastitis and generally for treatment of the systemic signs associated with mastitis. (J303.7.w1, P55.1998.w1)
  • In sheep, treatment of acute gangrenous mastitis is generally not considered economically worthwhile for commercial ewes. (J15.23.w1)
  • Many cases of mastitis in ewes are not detected until they have become chronic infections. (J15.23.w1)

• Reasons for Failure to Provide Pain Relief
• Assessment of Pain in Ruminants