Research Paper| Volume 41, ISSUE 3, P305-311, May 2014

Thermal and mechanical nociceptive threshold testing in pregnant sheep



      Analgesic regimes were compared in pregnant ewes after laparotomy by measuring thermal (TT) and mechanical (MT) nociceptive thresholds.

      Study design

      Prospective randomised experimental study.


      Pregnant ewes at 121 days gestation underwent laparotomy as part of another research project.


      Thermal and mechanical thresholds were measured before, and 2, 6, 24 and 48 hours after surgery. Thermal stimuli were delivered to the lateral aspect of the metatarsus via a skin-mounted probe, and mechanical stimuli to the contralateral site via a pneumatically driven 1.5 mm diameter pin. Each test was performed five times, alternating thermal and mechanical stimuli, with ten minutes between thermal stimuli. At the end of surgery ewes received either: 75 μg hour−1 transdermal fentanyl patch (medial thigh) (group FP) (n = 8), or 3 μg kg−1hour−1 intra-peritoneal medetomidine via an osmotic pump (group IPM) (n = 8) inserted immediately prior to closure. Data were analysed using the Kruskal–Wallis RS Test (p < 0.05). Once a significant effect was identified, pairwise comparisons were performed using paired Wilcoxon RS tests. To compensate for multiple hypotheses testing, p < 0.005 was considered significant.


      Prior to surgery mean ± SD TT was 56.1 ± 5.0 °C (FP) and 55.6 ± 5.0 °C (IPM); MT was 5.3 ± 2.6 N (FP) and 8.0 ± 5.0 N (IPM). In FP there was no significant change in either TT or MT over time. In IPM there was no significant change in MT over time but TT increased at two hours to 59.2 ± 3.0 °C (p = 0.003). Skin temperature (ST) ranged from 33.0 to 34.7 °C and did not change over time. There were no significant differences between groups in TT, MT or ST.

      Conclusions and clinical relevance

      Administration of intra-peritoneal medetomidine (3 μg kg−1hour−1) by an osmotic pump increases the thermal nociceptive threshold in the immediate post operative period in pregnant sheep, suggesting that this agent may have a role in providing post-operative analgesia.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Veterinary Anaesthesia and Analgesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ahern BJ
        • Soma LR
        • Boston RC
        • et al.
        Comparison of the analgesic properties of transdermally administered fentanyl and intramuscularly administered buprenorphine during and following experimental orthopedic surgery in sheep.
        Am J Vet Res. 2009; 70: 418-422
        • Ahern BJ
        • Soma LR
        • Rudy JA
        • et al.
        Pharmacokinetics of fentanyl administered transdermally and intravenously in sheep.
        Am J Vet Res. 2010; 71: 1127-1132
        • Australian Government
        Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. 7th edn. National Health and Medical Research Council, Canberra, Australia2004
        • Beecher HK
        The measurement of pain: prototype for the quantitative study of subjective responses.
        Pharmacol Rev. 1957; 9: 59-209
        • Bergadano A
        • Andersen OK
        • Arendt-Nielsen L
        • et al.
        Quantitative assessment of nociceptive processes in conscious dogs by use of the nociceptive withdrawal reflex.
        Am J Vet Res. 2006; 67: 882-889
        • Bergadano A
        • Andersen OK
        • Arendt-Nielsen L
        • et al.
        Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine.
        Vet Anaesth Analg. 2009; 36: 261-272
        • Dixon MJ
        • Taylor PM
        • Steagall PVM
        • et al.
        Development of a pressure nociceptive threshold testing device for evaluation of analgesics in cats.
        Res Vet Sci. 2007; 82: 85-92
        • Dixon MJ
        • Taylor PM
        • Slingsby L
        • et al.
        A small, silent, low friction, linear actuator for mechanical nociceptive threshold testing in veterinary research.
        Lab Anim. 2010; 44: 247-253
        • Djouhri L
        • Lawson SN
        Abeta fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals.
        Brain Res Rev. 2004; 46: 131-145
        • Fitzpatrick J
        • Scott M
        • Nolan A
        Assessment of pain and welfare in sheep.
        Small Rumin Res. 2006; 62: 55-61
        • Grant C
        • Upton RN
        Comparison of the analgesic effects of xylazine in sheep via three different administration routes.
        Aust Vet J. 2004; 82: 304-307
        • Grant C
        • Summersides GE
        • Kuchel TR
        A xylazine infusion regimen to provide analgesia in sheep.
        Lab Anim. 2001; 35: 277-281
        • Hoffmann MV
        • Kästner SB
        • Kietzmann M
        • et al.
        Contact heat thermal threshold testing in beagle dogs: baseline reproducibility and the effect of acepromazine, levomethadone and fenpipramide.
        BMC Vet Res. 2012; 8: 206
        • Hothersall B
        • Caplen G
        • Nicol CJ
        • et al.
        Development of mechanical and thermal nociceptive threshold testing devices in unrestrained birds (broiler chickens).
        J Neurosci Methods. 2011; 201: 220-227
        • Hunter JC
        • Fontana DJ
        • Hedley LR
        • et al.
        Assessment of the role of α2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice.
        Br J Pharmacol. 1997; 122: 1339-1344
        • Jedruch J
        • Gajewski Z
        • Ratajska-Michalczak K
        Uterine motor responses to an alpha 2-adrenergic agonist medetomidine hydrochloride in the bitches during the end of gestation and the post-partum period.
        Acta Vet Scand Suppl. 1989; 85: 129-134
        • Kästner SBR
        A2-agonists in sheep: a review.
        Vet Anaesth Analg. 2006; 33: 79-96
        • Kemp MW
        • Saito M
        • Newnham JP
        • et al.
        Preterm birth, infection, and inflammation advances from the study of animal models.
        Reprod Sci. 2010; 17: 619-628
        • Lizarraga I
        • Chambers JP
        Involvement of opioidergic and alpha2-adrenergic mechanisms in the central analgesic effects of non-steroidal anti-inflammatory drugs in sheep.
        Res Vet Sci. 2006; 80: 194-200
        • Lizarraga I
        • Chambers JP
        Use of analgesic drugs for pain management in sheep.
        N Z Vet J. 2011; 60: 87-94
        • Lizarraga I
        • Chambers JP
        • Johnson CB
        Prevention of N-methyl-d-aspartate-induced mechanical nociception by intrathecal administration of ketoprofen and ketamine in sheep.
        Anesth Analg. 2008; 107: 2061-2067
        • Love EJ
        • Murrell J
        • Whay HR
        Thermal and mechanical nociceptive threshold testing in horses: a review.
        Vet Anaesth Analg. 2011; 38: 3-14
        • Murdoch FR
        • Maker GL
        • Nitsos I
        • et al.
        Intra-peritoneal medetomidine: a novel analgesic strategy for post-operative pain management in pregnant sheep.
        Lab Anim. 2013; 47: 66-70
        • Nolan A
        Pain: its nature and management in man and animals, international congress and symposium series.
        in: Morton D Patterns and management of pain in animals. Royal Society of Medicine Press, Abingdon, UK2000: 93-100
        • Nolan A
        • Livingston A
        • Morris R
        • et al.
        Techniques for comparison of thermal and mechanical nociceptive stimuli in the sheep.
        J Pharmacol Methods. 1987; 17: 39-49
        • Nolan A
        • Livingston A
        • Waterman A
        Investigation of the antinociceptive activity of buprenorphine in sheep.
        Br J Pharmacol. 1987; 92: 527-533
        • Rasmussen DB
        • Fogsgaard K
        • Røntved CM
        • et al.
        Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis.
        Acta Vet Scand. 2011; 53: 1-7
        • Robertson SA
        • Taylor PM
        • Lascelles BDX
        • et al.
        Changes in thermal threshold response in eight cats after administration of buprenorphine, butorphanol and morphine.
        Vet Rec. 2003; 153: 462-465
        • Sandercock DA
        • Gibson IF
        • Brash HM
        • et al.
        Development of a mechanical stimulator and force measurement system for the assessment of nociceptive thresholds in pigs.
        J Neurosci Methods. 2009; 182: 64-70
        • Talke PO
        • Traber DL
        • Richardson CA
        • et al.
        The effect of alpha 2 agonist-induced sedation and its reversal with an alpha 2 antagonist on organ blood flow in sheep.
        Anesth Analg. 2000; 90: 1060-1066
        • Taylor PM
        • Robertson SA
        • Dixon MJ
        Evaluation of the use of thermal thresholds to investigate NSAID analgesia in a model of inflammatory pain in cats.
        J Feline Med Surg. 2007; 9: 313-318
        • Waterman AE
        • Livingston A
        • Amin A
        The antinociceptive activity and respiratory effects of fentanyl in sheep.
        Vet Anaesth Analg. 1990; 17: 20-23