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Table 3 Summary of publication year, reference (Ref.), painful procedures/condition/disease, grouping and age of animals, sampling times, Substance P (SP) concentrations and conclusion of 11 studies using SP for the evaluation of nociception in adult cattle. The administration of local anesthesia (LA) is given in the same column as the grouping of animals. Data was not extractable from 9.1% (n = 1) of papers 

From: Substance P concentrations in the blood plasma and serum of adult cattle and calves during different painful procedures and conditions – a systematic review

Year

Ref

Procedure/Disease with/without LA

Grouping

Weight/Age/Lactation

Samplingin Times and Assay Platform

SP Concentrations

Conclusions

Lameness

2015

[49]

Oligofructose induced-lameness

- Treatment (13 g/kg BW oligofructose orally, n = 6)

- Control (n = 6)

- no LA

250 to 300 kg

- 48 and 24 h before induction of lameness

- 6, 12, 24, 36, and 48 h after induction of lameness

- ELISA

Mean plasma SP concentrations

Control 0.26 to 0.42 ng/mL

12 h after lameness induction:

Treatment group 2.20 ± 0.47 ng/mL

Mean plasma SP concentrations increased significantly (p < 0.05) 6 h after lameness was induced (treatment group), with a peak 12 h, and decreasing after 48 h after induction. Plasma SP concentrations differed significantly (p < 0.001) at every time point after baseline between treatment and control group

2019

[50]

Ampothericin B induced-lameness

- L + F (lameness + flunixin, n = 10)

- L + P (lameness + placebo, n = 10)

- S + P (sham + placebo, n = 10)

- no LA

2nd or 3rd lactation

- 6 h before induction of lameness

- 1, 2, 8, 24, 48, 72, 96, and 120 h after lameness induction

- RIA

Mean SP concentrations

L + P 84.59 pg/mL; 95% CI: 73.12 to 96.05 pg/mL

L + F 81.89 pg/mL; 95% CI: 72.16 to 91.62 pg/mL

S + P 70.59 pg/mL; 95% CI: 55.72 to 85.46 pg/mL

The L + P group had similar SP concentrations to the L + F (topical flunixin meglumine (3.33 mg/kg) for 3 days every 24 h) and S + P group

[51]

Lameness

- MS 0 (n = 25)

- MS 1 (n = 25)

- MS 2 (n = 25)

- MS 3 (n = 25)

(on the basis of mobility scoring (MS))

- no LA

1st to 6th lactation, 400 to 500 kg

- 1 sample at last follow up visit

- ELISA

Mean SP Concentrations

MS 0 0.25 ± 0.09 ng/mL

MS 1 0.21 ± 0.13 ng/mL

MS 2 0.42 ± 0.12 ng/mL

MS 3 0.61 ± 0.12 ng/mL

The mean SP concentrations increased linearly with the increase of MS score. Animals in M3 showed a significant (p = 0.000043) increase in SP concentrations compared with MS 0 animals

2020

[52]

Ampothericin B induced-lameness

- LAME + FLU (flunixin, n = 12)

- LAME + MEL (meloxicam, n = 12)

- LAME + PLBO (placebo, n = 12)

- SHAM + PLBO (not lame and placebo, n = 12)

- no LA

 

- 24 h before induction of lameness

- 0, 2, 8, 24, 48, 72, 96 and 120 h after induction of lameness

- RIA

Log LSM SP concentrations

LAME + MEL 2.03 pg/mL (95% CI: 1.93, 2.14 pg/ mL)

LAME + FLU 2.00 pg/mL (95% CI: 1.90, 2.11 pg/mL)

LAME + PBLO 1.98 pg/mL (95% CI: 1.88, 2.09 pg/mL

SHAM + PBLO 2.07 pg/mL (95% CI: 1.97, 2.17 pg/ mL

There were no differences between treatments (flunixin meglumine at 2.2 mg/kg BW IV,

Meloxicam at1 mg/kg BW orally, or a placebo 2 × every 24 h) or over time for any of the investigated time points

Diseases

2018

[53]

Clinical Metritis

- CM (Clinical metritis, n = 70)

- NO-CM (no clinical metritis, n = 88)

- no LA

 

- Day 1

- RIA

Circulating SP Concentrations

CM cows 41.15 ± 5.38 pg/mL

NO-CM cows 37.73 ± 5.41 pg/mL

Circulating SP concentrations were significantly (p = 0.01) higher in CM compared with NO-CM cows

[54]

Intrapartum Uterine Torsion

- Intrapartum uterine torsion (n = 20)

- Healthy controls (n = 36)

- Intrapartum without uterine torsion (n = 15)

- no LA

 

- Day 1

- ELISA

Serum SP concentrations

Control 37.9 ± 10.5 pg/mL

Intrapartum (no uterine torsion) 49.6 ± 14.5 pg/mL

Intrapartum (uterine torsion) 32.8 ± 14.1 pg/mL

The SP concentrations were higher in intrapartum cows compared with cows with uterine torsion; also, SP concentrations were significantly (p < 0.01) higher in intrapartum compared with healthy cows

2020

[55]

Parturition

PRIM (pimiparous, n = 47) and MULT (multiparous, n = 105), also EUT (eutocia) and DYS (dystocia) divided into the following treatment groups:

- ASP (acetylsalicylic acid, n = 76, including 38 DYS and 38 EUT)

- PLC (placebo, n = 76, including 38 DYS and 38 EUT)

categorized as

- NO-EVT (no disease)

- SI-EVT (single disease)

- MU-EVT (multiple diseases)

- no LA

 

- 12, 24, 36, and 48 h before parturition (before each treatment administration (4 consecutive treatments at 12 h interval with either acetylsalicylic acid (100 mg/kg orally) or a placebo)—168 ± 72 h after parturition

- RIA

Circulating SP Concentrations

ASP 56.76 pg/mL, 95% CI: 55.16–58.41

PLC 55.95 pg/mL, 95% CI: 54.36–57.57

At 168 ± 72 h after parturition

DYS 64.99 pg/mL, 95% CI: 62.08–68.06

EUT 60.33 pg/mL, 95% CI: 57.65–63.15

PRIM 57.62 pg/mL, 95% CI: 55.62–59.68

MULT 55.11 pg/mL, 95% CI: 53.83–56.42

There was no difference in circulating SP concentrations between both treatments. SP concentrations increased after parturition with the highest levels at 168 h. An interaction (p = 0.07) between calving ease and hour after calving was observed; DYS cows showed higher concentrations of SP at 168 ± 72 compared with EUT (p = 0.02), and PRIM cows showed higher circulating SP concentrations compared with MULT cows (p = 0.04). There was no difference in SP concentrations between animals with a different number of clinical disease events

Surgeries

2012

[56]

Electroejaculation

- EEJ

- Probed, no EEJ

- Control

n = 9, each bull receiving each treatment

- no LA

14.15 ± 0.14 months, 501.9 ± 14.3 kg

- 60 and 30 min before, treatment

- 0 min and immediately after treatment

- 10, 20, 30, 45, 60, 75, 90, and 120 min after treatment

- ELISA

MEAN and SEM plasma SP Concentrations

Controll Bulls 93.4 ± 17.2 pg/mL

Probed Bulls 79.1 ± 17.2 pg/mL

Bulls after Electroejaculation 77.2 ± 17.2 pg/mL

Mean plasma SP concentrations were not different between groups. An effect of time (p < 0.0001) could be observed, but no effect of treatment. Also, there was no interaction of treatment and time on SP concentrations

2020

[57]

Ovariectomy

- PALP (sham procedure, n = 14)

- SPAY (ovariectomy, n = 15)

- BXKM (spay + NSAID, n = 15; Combination of butorphanol (0.01 mg/kg BW), xylazine (0.02 mg/kg BW), and ketamine (0.04 mg/kg BW) IM 5 min pre OP and oral meloxicam (1 mg/kg) immediately before surgery

- no LA

322 ± 27.0 kg

- D-1

- D0 (at time of procedure)

- 1, 2, and 4 h after procedure

- Day 1, 2, 4, and 7 after procedure

- Competitive Immunoassay

LSM plasma SP Concentrations

PALP 78.7 pg/mL

SPAY 79.8 pg/mL

BXKM 78.6 pg/mL

Regarding SP concentrations, there was no treatment or treatment x interaction effect between groups

[58]

Endoscopic Abomasopey

- CON (placebo, n = 14)

- XYL (xylazine, n = 14)

- local infiltration of skin with 2% procain hydrochloride for both groups

6.0 ± 2.0 years, 662.3 ± 110.7 kg

-180 min (Baseline) before surgery

- at the start of surgery

- 15, 30, 45, 60, 90, 120, and 180 min after start of the surgery

- 24 h after the start of the surgery

- ELISA

Mean plasma SP Concentrations

Baseline Values

CON 555.37 ± 252.77 pg/mL

XYL 490.60 ± 219.62 pg/mL

There was no significant difference between plasma SP concentrations between CON and XYL (0.02 mg xylazine IV 15 min before the start of the surgery) at any time point

Other

2014

[59]

Long distance transportation

- MEL (meloxicam)

- PLACEBO

- no LA

15 to 17 months, 201 to 465 kg

Baseline at Time 0, immediately before treatment and 24 and 144 h after baseline sampling

- RIA

No extractable numerical data

SP concentrations increased significantly (p < 0.0026) after transportation. There was no treatment, or treatment x time interaction, as well as no association between MEL (Meloxicam, at 1 mg/kg BW orally) and SP

  1. BW Bodyweight, IV Intravenously, OP Surgery, SC Subcutaneously, RIA Radioimmunoassay, ELISA Enzyme Linked Immunosorbent Essay