FareWellDock

Ending tail docking & tail biting in the EU

Hazard characterization & exposure assessment of a major pig welfare problem

FareWellDock

Goals

§ Estimate relative harms associated with tail docking & tail biting

§ Evaluate efficacy of preventive measures against tail biting to reduce need

for docking

§ Supply information for quantitative risk assessment & development of a

EU non-docking policy

FareWellDock – WP 1• Short & long term effects of tail docking & tail biting

– Evaluation of acute & chronic pain of tail docking

– Effect of NSAIDs in relieving pain from tail docking

– Evaluation on human-animal interactions of tail docking

– Evaluation of chronic pain due to tail injury in growing pigs

To assess it, you need to define it…

‘Pain is an unpleasant sensory & emotional

experience associated with actual or potential

tissue damage’ International Society for the Study of Pain

To assess it, you need to define it…

‘Pain is an unpleasant sensory & emotional

experience associated with actual or potential

tissue damage’ International Society for the Study of Pain

This is critical for understanding both the nociceptive pathways

involved, and the potential pathological changes that can occur

To assess it, you need to define it…

‘Pain is an unpleasant sensory & emotional

experience associated with actual or potential

tissue damage’ International Society for the Study of Pain

This is critical, as the ‘experience’ of pain has the greatest

impact on pig welfare

Assess in all aspects of pain

Cell MolecularGene

expressionSensory

NociceptionQuantitative

sensory testing

Physiological Thermography

BehaviouralSpontaneous

behaviour

Whole Animal

Facial expressions

Grimace Scales

Emotional

Types of pain studied• We were interested in both:

– Acute: short-duration, provoked by specific injury, serving a

useful biological purpose (i.e. protection while healing)

– Chronic: longer-duration (i.e. beyond healing), more of a

psychological state, serving no biologic purpose

Quantitative sensory testing• Application of standardised noxious stimuli to induce

a reflex response

– Mechanical, thermal or electrical…

– Used to measure nociceptive (i.e. sensory) thresholds

• Wide range of methods used

– Choice depends on type of pain (acute / chronic) modeled

• Elicits specific behavioural response (e.g. withdrawal)

– Latency & frequency of response routinely measured

– Intensity of stimulus required to elicit a response

• Easy to use, but difficult to master…

Model of tail docking

1Scientific RepoRts | 7: 4827 | DOI:10.1038/s41598-017-05404-y

www.nature.com/scientificreports

Characterization of short- and long-term mechanical sensitisation following surgical tail amputation in pigsPierpaolo Di Giminiani 1, Sandra A. Edwards1, Emma M. Malcolm1, Matthew C. Leach1, Mette S. Herskin3 & Dale A. Sandercock2

Commercial pigs are frequently exposed to tail mutilations in the form of preventive husbandry procedures (tail docking) or as a result of abnormal behaviour (tail biting). Although tissue and nerve injuries are well-described causes of pain hypersensitivity in humans and in rodent animal models, there is no information on the changes in local pain sensitivity induced by tail injuries in pigs. To determine the temporal profile of sensitisation, pigs were exposed to surgical tail resections and mechanical nociceptive thresholds (MNT) were measured in the acute (one week post-operatively) and in the long-term (either eight or sixteen weeks post-surgery) phase of recovery. The influence of the degree of amputation on MNTs was also evaluated by comparing three different tail-resection treatments (intact, ‘short tail’, ‘long tail’). A significant reduction in MNTs one week following surgery suggests the occurrence of acute sensitisation. Long-term hypersensitivity was also observed in tail-resected pigs at either two or four months following surgery. Tail amputation in pigs appears to evoke acute and sustained changes in peripheral mechanical sensitivity, which resemble features of neuropathic pain reported in humans and other species and provides new information on implications for the welfare of animals subjected to this type of injury.

Tissue and nerve injuries caused by surgical procedures lead to acute peripheral sensitisation of the affected area, with a possible involvement of central pain-processing pathways. Animal models of post-incisional pain have for a long time provided a valuable platform to understand the mechanisms mediating alterations in nociceptive thresholds observed shortly after surgical incision or for more sustained periods of time (e.g. days) afterwards1–4. Recently, post-operative pain has been investigated in pigs5, reporting significant sensitisation to mechanical noxious stimuli (i.e. von Frey stimulation) induced by skin and muscle incision in the caudal end of the lower back. It is well recognised that in situations where there is resection of peripheral nerves the formation of trau-matic neuromas (a tangle of truncated neural fibres and connective tissue) can occur, which in humans can be a significant cause of pain6, 7. Traumatic neuromas are particularly common in the case of amputation or surgical removal of body parts such as limbs, breasts, rectum, penis, testicles, eye, tongue or teeth8. This type of trauma can be associated with the phenomenon of residual stump pain and phantom limb pain, a physiological and psychological percept classified as a neuropathic pain state8, with painful symptomatic neuromas observed in 10–25% of amputees9.

Neuropathic pain refers to ‘pain arising as a direct consequence of a lesion or disease affecting the soma-tosensory system10, and its physiological manifestation has been investigated in rodent models; however it is yet unknown if a similar phenomenon occurs in pigs following tail amputation and this is an important question in the current debate on animal welfare issues. The aetiology of this particular type of neuropathic pain is uncer-tain; however persistent ectopic discharge of axons within the neuroma has been suggested as the most plausible mechanism11.

1 c oo of ricu ture oo an ura De e opment ewcast e ni ersity ewcast e upon yne 1 7 United Kingdom. Animal and Veterinary Science Research Group, Scotland’s Rural College (SRUC), West Mains

oa in ur 1 4 nite in om. 3Aarhus University, Department of Animal Science, Au-Foulum, Tjele, Denmark. Correspondence and requests for materials should be addressed to P.D.G. (email: Pierpaolo.Di-Giminiani@newcastle.ac.uk)

Received: 28 February 2017

Accepted: 26 May 2017

Published: xx xx xxxx

OPEN

Di Giminiani et al. (2017) Nature Scientific Reports 7: 4827-4835.

Significant decrease in threshold of sensitivity

at both one week & 16 weeks post-surgery

Thermography• Increasingly used animal welfare assessment tool

– Rapid & non-invasive method of assessing surface temperature

– Image & live video can be used

• Only 1 published study for pain in cattle*

• Utilising infra-red thermography to assess:

– Inflammation & tissue regeneration over time resulting from tail-docking

ThermographyIn 17-week old pigs, one week following tail

resection surgery (i.e. tail biting model):

Following mechanical stimulation of the tail, superficial

skin temperature:

in intact tails

in resected tails

In 17-week old pigs, tail-docked (as a neonate):

Following mechanical stimulation of the tail, superficial

skin temperature:

in intact tails

in docked tails

Suggests long term changes in sensory processing = Possible implications for pain

Di Giminiani et al. (2019) In Prep

Suggests increased inflammation, which is likely to be associated with pain

Chronic pain & tail docking• Tail amputation (i.e. docking) can lead to chronic pain

– Neuroma formation on peripheral nerves

– Molecular changes in the pain pathways

Gene expression profiles

Sandercock et al. (2018) In Prep

Significant gene expression responses to tail amputation at

1 & 4 months following neonatal docking or juvenile tail resection

Tissue matrix remodelling: SERPINB2, ARG1

Modulation of synaptic transmission: PENK, OPRM1, NPY, GAL

Inflammatory response: PTGS2, SST

Neurogenesis:NRN1, ATF3

Regulation of membrane potential: KCNB2, KCNIP3, ASIC1, ADORA1, HTR2A

• Potential implications for long-term/chronic pain

– Tail amputation produces significant changes in gene expression in caudal dorsal root ganglia up to 4 months after the cause of injury

– Network analysis revealed 2 highly correlated gene expression clusters related to (i) wound healing & (ii) neuronal function

– Observations consistent with compensatory responses in sensory neurons linked to sustained tissue inflammation in the tail stump

– These gene expression data match the long-term changes in nociceptive sensitivity

• Tail amputation injury causes acute & sustained changes in sensory nerve function associated with prolonged pain sensitivity • Possibly linked to neuropathic pain, having implications for pig welfare

Gene expression profiles

Grimace scales• Gold standard assessment for non-verbal humans

– Effective, rapid & easy to carry out using a limited number of indicators

– Seems to represents ‘generic’ response to pain & uses the human tendency to fixate on faces

• Considered to be directly linked to emotional state…

• Evolutionarily conserved across human & non-human species

Grimace scales• Gold standard assessment for non-verbal humans

– Effective, rapid & easy to carry out using a limited number of indicators

– Seems to represents ‘generic’ response to pain & uses the human tendency to fixate on faces

• Considered to be directly linked to emotional state…

• Evolutionarily conserved across human & non-human speciesChambers & Mogil (2015) Pain Pictured 156: 798-799

Current grimace scalesMouse (MGS) Langford et al. (2010) Nature Methods 7: 447 ?Rat (RGS) Sotocinal et al. (2011) Molecular Pain 7: 55 ?Rabbit (RbtGS) Keating et al. (2012) PLoS ONE 7: e44437 ?Horse (HGS) Dalla Costa et al. (2013) PLoS ONE 9: e92281 ?Horse (EPF) Gleerup et al. (2014) Veterinary Anaesthesia and

Analgesia 42, 103–114 ?Cat Holden et al. (2014) Journal of Small Animal Practice 55:

615-621 ?Sheep (SPFS) McLennan et al. (2016) Applied Animal Behaviour

Science 176: 19–26

Cow (CPS)* Gleerup et al. (2014) Applied Animal Behaviour Science 171: 25–32 ?

Piglet grimace scale – Development

Piglet grimace scale – Results

Spontaneous pain behaviours

• Developed & validated through research

– Pain causes a change from before to after painful event

– Effective analgesia reduces these changes

• Behaviour-based indices are increasingly being used

– Rabbits, rodents, dogs, cats, lambs, calves & pigs

• Considered more effective than general methods

– Immediate cage/pen side assessment (not retrospective)

– Growing evidence of relationship between pain & behaviour

• Non-invasive but require training to use effectively

Spontaneous behaviour

General behaviours

Di Giminiani et al. (2019) In Prep

Spontaneous behaviour

General behaviours

Tail position

Di Giminiani et al. (2019) In Prep

ConclusionsTail docking & tail-biting are associated with both acute & chronic

changes in sensory & potentially emotional aspects of pain

Sensory

• Increases in nociceptive thresholds

• Changes in sensory processing

• Gene expression profiles

• Potentially thermography

Emotional

• Increases in spontaneous pain

behaviours

• Increases in grimace scale

scores

Thank you listening

Matthew.leach@newcastle.ac.uk

Questions?