The Veterinary Clinics of North America

There is great practical need for a dependable method of assessing effects of analgesics on experimental pain in man. Past use of threshold pain has not provided such a method. A technique, called here the submaximum effort tourniquet technique, was developed to produce experimental pain in man which simulates the duration and severity of pathologic pain more closely than earlier experimental methods. Pain was produced by having the subject squeeze a hand exerciser 20 times after a tourniquet had been inflated around his upper arm. Under appropriately controlled drug and placebo conditions, 45 male subjects (experiments I, II, III combined) were studied to determine the amount of time required for pain to build up to levels designated as slight, moderately distressing, very distressing and unbearable. Intravenous morphine, 10 mg/70 kg b.wt., was found to allay significantly the development of moderately distressing, very distressing and unbearable pain. There were indications that the 10-mg dosage of morphine might also be capable of allaying development of slight pain and that the 5-mg dosage might be capable of allaying development of unbearable pain, but these effects were not conclusive. Although the effect of 10 mg of morphine was more dependable ( i.e. , more statistically significant) at the higher pain levels than at the lower levels, the magnitude of the morphine effect was approximately a fixed multiple of the placebo score. Indeed, the largest morphine effect (expressed as percent of the placebo effect) was on the lowest pain level. When averaged for the four pain levels, the 10-mg dosage of morphine prolonged pain tolerance about 70%. It was concluded that appropriate use of the submaximum tourniquet technique produces a type of experimental pain which is responsive to the analgesic effects of 10 mg of intravenous morphine.

An experimental pain method sensitive to morphine in man: the submaximum effort tourniquet technique

The concept that the immune system can communicate with peripheral sensory neurons to modulate pain is based mostly on documented interactions between opioid ligands and receptors. Such findings may have broad implications for the development of safer pain medication. Innovative strategies take into account that analgesics should be particularly active in pathological states rather than producing a general suppression of the central nervous system, as with conventional morphine- or cannabinoid-like drugs. Inflammation of peripheral tissue leads to increased functionality of opioid receptors on peripheral sensory neurons and to local production of endogenous opioid peptides. In addition, endocannabinoids were detected in leukocytes, but their role in pain modulation has yet to be addressed. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing immune cells to sites of painful injury, and the augmentation of peripheral ligand and receptor synthesis (e.g., by gene therapy). Similar approaches may be pursued for cannabinoids. The ultimate goal is to avoid detrimental side effects of currently available analgesics such as respiratory depression, cognitive impairment, addiction, gastrointestinal bleeding, and thromboembolic complications.

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

Recent studies have demonstrated that horses can recognize humans based simply on visual information. However, none of these studies have investigated whether this involves the recognition of the face itself, or simply identifying people from non-complex external clues, such as hair color. To go beyond this we wanted to know whether certain features of the face were indispensable for this recognition (e.g., colors, hair or eyes). The 11 horses in this study had previously learned to identify four unfamiliar faces (portrait view and in color) presented repeatedly on a screen. We thus assessed whether they were able to identify these same faces spontaneously when they were presented in four other conditions: profile view, black and white, eyes hidden, changed hairstyle. The horses' performances remained higher than chance level for all the conditions. In a choice test under real conditions, they then approached the people whose face they had learned more often than unknown people. In conclusion, when considering all the individuals studied, no single facial element that we tested appears to be essential for recognition, suggesting holistic processing in face recognition. That means horses do not base their recognition solely on an easy clue such as hair color. They can also link faces from photographs with people in real life, indicating that horses do not process images of faces as simple abstract shapes.

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Human Face Recognition in Horses: Data in Favor of a Holistic Process.

Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/vaa.12212

An equine pain face

Pain evaluation in dairy cattle

Summary

Pain management is dependent on the quality of the pain evaluation. Ideally, pain evaluation is objective, pain-specific and easily incorporated into a busy equine clinic. This paper reviews the existing knowledge base regarding the identification and quantification of pain in horses. Behavioural indicators of pain in horses in the context of normal equine behaviour, as well as various physiological parameters potentially useful for pain evaluation, are discussed. Areas where knowledge is sparse are identified and a new equine pain scale based on results from all reviewed papers is proposed. Finally, the most important considerations in relation to the implementation of a pain scale in a hospital setting are discussed.

Recognition and quantification of pain in horses: A tutorial review

Objective The objective of this study was to investigate the existence of an equine pain face and to describe this in detail. Study design Semi-randomized, controlled, crossover trial. Animals Six adult horses. Methods Pain was induced with two noxious stimuli, a tourniquet on the antebrachium and topical application of capsaicin. All horses participated in two control trials and received both noxious stimuli twice, once with and once without an observer present. During all sessions their pain state was scored. The horses were filmed and the close-up video recordings of the faces were analysed for alterations in behaviour and facial expressions. Still images from the trials were evaluated for the presence of each of the specific pain face features identified from the video analysis. Results Both noxious challenges were effective in producing a pain response resulting in significantly increased pain scores. Alterations in facial expressions were observed in all horses during all noxious stimulations. The number of pain face features present on the still images from the noxious challenges were significantly higher than for the control trial (p = 0.0001). Facial expressions representative for control and pain trials were condensed into explanatory illustrations. During pain sessions with an observer present, the horses increased their contact-seeking behavior. Conclusions and clinical relevance An equine pain face comprising ‘low’ and/or ‘asymmetrical’ ears, an angled appearance of the eyes, a withdrawn and/or tense stare, mediolaterally dilated nostrils and tension of the lips, chin and certain facial muscles can be recognized in horses during induced acute pain. This description of an equine pain face may be useful for improving tools for pain recognition in horses with mild to moderate pain.

The equine pain face

Objective—To compare the effects of intra-articular (IA) versus IV administration of morphine on local and systemic inflammatory responses in horses with experimentally induced acute synovitis. Animals—8 horses. Procedures—Each horse received the following 2 treatments 4 hours after synovitis was induced: IA administration of morphine (0.05 mg/kg) with IV administration of 1 mL of saline (0.9% NaCl) solution/100 kg, and IA administration of 1 mL of saline solution/100 kg with IV administration of morphine (0.05 mg/kg). Treatments were administered in randomized order with a washout period of 3 weeks between treatments. Before each treatment, aseptic synovitis was induced by injection of lipopolysaccharide into a radiocarpal joint. For the second treatment, the contralateral radiocarpal joint was selected. Joint swelling and skin temperature over the treated joints were recorded. Clinical examinations were performed, and blood WBC count, serum amyloid A (SAA) concentration, serum cortisol concentration, sy...

Karina B. Gleerup

Papers

An equine pain face

Pain evaluation in dairy cattle

Recognition and quantification of pain in horses: A tutorial review

The equine pain face

Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis