The opioid component of the effect of the lacrimal glands on wound healing

Naloxone partially inhibited skin wound contraction and completely blocked acceleration of wound healing in rats with stimulated lacrimal glands. Endorphins were detected in lacrimal glands. Alteration of functional activity of the lacrimal glands produces a considerable effect on pain sensitivity and endorphin blood concentration. Opioid peptides have a considerable effect on the functioning of the lacrimal apparatus and are involved in injury-induced reactions, regulating pain sensitivity, structural homeostasis and producing an anti-stress effect.     

Body Site Variation of Heat Pain Sensitivity

Thirty-two healthy human subjects provided thresholds for the perception of slight and moderate heat pain. Four body sites were tested bilaterally: thenar eminence of the hand, plantar surface of the foot, dorsolateral forearm, and lateral calf. Thresholds for the glabrous skin of the hand and foot were significantly greater than thresholds for the hairy skin of the arm and leg, the average difference being 1.3°c. Laterality was not a statistically significant factor. Thresholds increased progressively over 2–4 weeks of repeated testing, resulting in values averaging 0.6°c higher in the later sessions. The difference between moderate and slight pain thresholds averaged 1.1°c, and was consistent across body sites and with repeated testing.

The threshold values were normally distributed across subjects. Considerable intersubject variability was observed for both slight and moderate pain thresholds, more so on glabrous than on hairy skin sites. In comparison, the distribution of right-left difference values was narrower, demonstrating less intrasubject versus intersubject variability.

The highly significant difference in thresholds between glabrous and hairy skin sites demonstrates the importance of skin type for heat pain sensitivity. In contrast, there was no significant difference in heat pain sensitivity between comparable sites on the upper versus lower extremities, or between left and right sides.     

Nociceptive sensitivity of the human skin during chronic psychoemotional stress

A comparative study of nociceptive sensitivity of the skin in 115 men (51 healthy and 64 with neurasthenia, a natural model of chronic psychoemotional stress) was undertaken with the aid of focused ultrasound. The group of patients revealed a distinct tendency for lowering of the pain threshold, weakening of adaptation to repeated presentation of a nociceptive stimulus of threshold strength, and sensitization. When these deviations were found in subjects, they were found to have a pain syndrome relatively more often. Since exposure to focused ultrasound of fairly high intensity involves primarily C afferents (not only cutaneous but also visceral nociceptors), it is suggested that the changes in nociceptive sensitivity observed in patients with neurasthenia are not confined to the skin, but extend also to the internal medium, facilitating the formation of a pain syndrome.I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint Petersburg. Translated from Neirofiziologiya, Vol. 24, No. 5, pp. 535–542, September–October, 1992.     

Sensory recovery in a split skin graft: pinprick or a thermal sensory analyzer?

Sensory return in a split skin graft is an important factor in the protection of this graft from injury. Hence, three tests were compared: (1) the standard pain test using a simple pin, (2) the cold pain test, and (3) the hot pain test. Both the hot and cold pain tests were performed using the thermal sensory analyzer device. Thirteen patients were investigated; all had split skin grafts applied directly onto deep fascia after malignant melanoma excision on the lower limb. The period after grafting ranged from 4 to 15 years, and the mean age was 46.5 years. The normal contralateral side of each patient was used as the control for that patient. The results were collected in simple data tables and were analyzed using paired t tables for small samples with the level of significance set at p < 0.05. The standard pain test demonstrated that the split skin grafts applied on deep fascia did not recover sensation, even 15 years after surgery (p < 0.001). The hot and cold pain tests were both in agreement with the standard pain test at p < 0.001 and p < 0.03, respectively. The standard pain test is usually performed, as described in this study, using a pin, which is cheap and readily available in any plastic surgery and burn clinic. However, the cold and hot pain tests as performed here using the thermal sensory analyzer device are accurate but are costly, cumbersome, and not available in all clinics except for highly specialized units. Hence, the author would like to dispel the myth that the standard pain test is inaccurate. This might be so in testing sensation in "normal" skin but not in testing the recovery of sensation in a skin graft.     

Contact Hypersensitivity to Oxazolone Provokes Vulvar Mechanical Hyperalgesia in Mice

The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition.     

Determining heat and mechanical pain threshold in inflamed skin of human subjects

In a previous article in the Journal of Visualized Experiments we have demonstrated skin microdialysis techniques for the collection of tissue-specific nociceptive and inflammatory biochemicals in humans. In this article we will show pain-testing paradigms that are often used in tandem with microdialysis procedures. Combining pain tests with microdialysis provides the critical link between behavioral and biochemical data that allows identifying key biochemicals responsible for generating and propagating pain.Two models of evoking pain in inflamed skin of human study participants are shown. The first model evokes pain with aid of heat stimuli. Heat evoked pain as described here is predominantly mediated by small, non-myelinated peripheral nociceptive nerve fibers (C-fibers). The second model evokes pain via punctuated pressure stimuli. Punctuated pressure evoked pain is predominantly mediated by small, myelinated peripheral nociceptive nerve fibers (A-delta fibers). The two models are mechanistically distinct and independently examine nociceptive processing by the two major peripheral nerve fiber populations involved in pain signaling.Heat pain is evoked with aid of the TSA II, a commercially available thermo-sensory analyzer (Medoc Advanced Medical Systems, Durham, NC). Stimulus configuration and delivery is handled with aid of specific software. Thermodes vary in size and shape but in principle consist of a metal plate that can be heated or cooled at various rates and for different periods of time. Algorithms assessing heat-evoked pain are manifold. In the experiments shown here, study participants are asked to indicate at what point they start experiencing pain while the thermode in contact with skin is heated at a predetermined rate starting at a temperature that does not evoke pain. The thermode temperature at which a subject starts experiencing pain constitutes the heat pain threshold.Mechanical pain is evoked with punctuated probes. Such probes are commercially available from several manufacturers (von Frey hairs). However, the accuracy of von Frey hairs has been criticized and many investigators use custom made punctuated pressure probes. In the experiments shown here eight custom-made punctuated probes of different weights are applied in consecutive order, a procedure called up-down algorithm, to identify perceptional deflection points, i.e., a change from feeling no pain to feeling pain or vice versa. The average weight causing a perceptional deflection constitutes the mechanical pain threshold.     

The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.

Cation channels in the DEG/ENaC family are proposed to detect cutaneous stimuli in mammals. We localized one such channel, DRASIC, in several different specialized sensory nerve endings of skin, suggesting it might participate in mechanosensation and/or acid-evoked nociception. Disrupting the mouse DRASIC gene altered sensory transduction in specific and distinct ways. Loss of DRASIC increased the sensitivity of mechanoreceptors detecting light touch, but it reduced the sensitivity of a mechanoreceptor responding to noxious pinch and decreased the response of acid- and noxious heat-sensitive nociceptors. The data suggest that DRASIC subunits participate in heteromultimeric channel complexes in sensory neurons. Moreover, in different cellular contexts, DRASIC may respond to mechanical stimuli or to low pH to mediate normal touch and pain sensation.     

Modulation of skin sensitivity by dynamic and isometric exercise in man

The effect of dynamic cycle ergometer exercise and isometric leg exercise on skin sensitivity was studied in man. Exercise was performed at different loads. Cutaneous sensitivity to innocuous and noxious thermal stimuli was tested using a contact thermostimulator and sensitivity to tactile stimuli was tested using electrical stimuli. During isometric exercise a segmental (the exercising limb), but not a multisegmental, phasic decrease of cutaneous thermal sensitivity to innocuous stimuli was found. At the isometric forces used the effect on tactile and heat pain sensitivity was not significant. During dynamic exercise a multisegmental, load-dependent decrease of sensitivity in all tested sensory modalities was found and this attenuation disappeared gradually after the end of exercise. In contrast to isometric exercise, the decrease of sensitivity produced by dynamic exercise was most evident in tactile sensitivity. The size of the stimulus area (7.9 vs 11.8 cm2) did not have a significant effect on the magnitude of the exercise-induced decrease of cutaneous thermal sensitivity to innocuous stimuli. It was concluded that underlying the modulation of skin sensitivity by dynamic and isometric exercise were mechanisms that were different, at least to a small extent. Isometric exercise produced a segmental modulation of skin sensitivity due to central neuronal mechanisms, independent of exercise-induced stress. Exercise-induced stress could have caused the modulation of skin sensitivity by dynamic exercise.     

Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

Degree of Skin Denervation and Its Correlation to Objective Thermal Sensory Test in Leprosy Patients

Background

Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST). Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods.

Methodology/Principal Findings

This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain). The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6) and 80.8% (SD = 24.9), respectively.

Conclusions/Significance

We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its diagnostic applicability, particularly in selected cases with only discrete sensory impairment, patients unable to perform the sensory test and especially those with nonspecific histopathological finds.     

Sex differences in thermal detection and thermal pain threshold and the thermal grill illusion: a psychophysical study in young volunteers

Background

Sex-related differences in human thermal and pain sensitivity are the subject of controversial discussion. The goal of this study in a large number of subjects was to investigate sex differences in thermal and thermal pain perception and the thermal grill illusion (TGI) as a phenomenon reflecting crosstalk between the thermoreceptive and nociceptive systems. The thermal grill illusion is a sensation of strong, but not necessarily painful, heat often preceded by transient cold upon skin contact with spatially interlaced innocuous warm and cool stimuli.

Methods

The TGI was studied in a group of 78 female and 58 male undergraduate students and was evoked by placing the palm of the right hand on the thermal grill (20/40 °C interleaved stimulus). Sex-related thermal perception was investigated by a retrospective analysis of thermal detection and thermal pain threshold data that had been measured in student laboratory courses over 5 years (776 female and 476 male undergraduate students) using the method of quantitative sensory testing (QST). To analyse correlations between thermal pain sensitivity and the TGI, thermal pain threshold and the TGI were determined in a group of 20 female and 20 male undergraduate students.

Results

The TGI was more pronounced in females than males. Females were more sensitive with respect to thermal detection and thermal pain thresholds. Independent of sex, thermal detection thresholds were dependent on the baseline temperature with a specific progression of an optimum curve for cold detection threshold versus baseline temperature. The distribution of cold pain thresholds was multi-modal and sex-dependent. The more pronounced TGI in females correlated with higher cold sensitivity and cold pain sensitivity in females than in males.

Conclusions

Our finding that thermal detection threshold not only differs between the sexes but is also dependent on the baseline temperature reveals a complex processing of “cold” and “warm” inputs in thermal perception. The results of the TGI experiment support the assumption that sex differences in cold-related thermoreception are responsible for sex differences in the TGI.

     

Modeling of nociceptor transduction in skin thermal pain sensation

All biological bodies live in a thermal environment with the human body as no exception, where skin is the interface with protecting function. When the temperature moves out of normal physiological range, skin fails to protect and pain sensation is evocated. Skin thermal pain is one of the most common problems for humans in everyday life as well as in thermal therapeutic treatments. Nocicetors (special receptor for pain) in skin play an important role in this process, converting the energy from external noxious thermal stimulus into electrical energy via nerve impulses. However, the underlying mechanisms of nociceptors are poorly understood and there have been limited efforts to model the transduction process. In this paper, a model of nociceptor transduction in skin thermal pain is developed in order to build direct relationship between stimuli and neural response, which incorporates a skin thermomechanical model for the calculation of temperature, damage and thermal stress at the location of nociceptor and a revised Hodgkin-Huxley form model for frequency modulation. The model qualitatively reproduces measured relationship between spike rate and temperature. With the addition of chemical and mechanical components, the model can reproduce the continuing perception of pain after temperature has returned to normal. The model can also predict differences in nociceptor activity as a function of nociceptor depth in skin tissue.     

The effects of stimulus location on the gating of touch by heat- and cold-induced pain

The influence of heat- and cold-induced pain on tactile sensitivity, a "touch gate", was measured under conditions in which the location of the noxious stimuli was varied with respect to the tactile stimulus applied to the thenar eminence of humans. Vibrotactile thresholds were measured in the absence of pain and during administration of a painful stimulus, with the stimulus frequencies selected to activate independently the four psychophysical channels hypothesized to exist in human glabrous skin. Heat-induced pain produced by spatially co-localizing the noxious stimuli with the tactile stimuli was found, on average, to elevate threshold amplitude by 2.2 times (6.7 dB). Co-localized, cold-induced pain raised the average thresholds by about 1.5 times (3.6 dB). Heat-induced pain presented contralaterally produced no change in vibrotactile sensitivity indicating that the effect is probably not due to attentional mechanisms. Ipsilateral heat-induced pain caused an elevation in tactile thresholds even when the noxious and non-noxious stimuli were not co-localized, and the effect may seem to require that the painful stimulus be within the somatosensory region defined possibly in terms of dermatomal organization. Thus the effect is probably related to somatotopic organization and is not peripherally mediated. A brief discussion as to the possible locus of the touch gate within the nervous system is also given.     

The effects of stimulus location on the gating of touch by heat- and cold-induced pain

The influence of heat- and cold-induced pain on tactile sensitivity, a "touch gate", was measured under conditions in which the location of the noxious stimuli was varied with respect to the tactile stimulus applied to the thenar eminence of humans. Vibrotactile thresholds were measured in the absence of pain and during administration of a painful stimulus, with the stimulus frequencies selected to activate independently the four psychophysical channels hypothesized to exist in human glabrous skin. Heat-induced pain produced by spatially co-localizing the noxious stimuli with the tactile stimuli was found, on average, to elevate threshold amplitude by 2.2 times (6.7 dB). Co-localized, cold-induced pain raised the average thresholds by about 1.5 times (3.6 dB). Heat-induced pain presented contralaterally produced no change in vibrotactile sensitivity indicating that the effect is probably not due to attentional mechanisms. Ipsilateral heat-induced pain caused an elevation in tactile thresholds even when the noxious and non-noxious stimuli were not co-localized, and the effect may seem to require that the painful stimulus be within the somatosensory region defined possibly in terms of dermatomal organization. Thus the effect is probably related to somatotopic organization and is not peripherally mediated. A brief discussion as to the possible locus of the touch gate within the nervous system is also given.     

Inducing Expectations for Health: Effects of Verbal Suggestion and Imagery on Pain,Itch, and Fatigue as Indicators of Physical Sensitivity

Research into placebo effects has convincingly shown that inducing positive outcome expectations can reduce pain and other physical sensations. However, the comparative effects of different expectation inductions, such as verbal suggestion or mental imagery, and their generic effects on physical sensitivity, to different sensations such as pain, itch, and fatigue, are still largely unknown. In the current study, we assessed the individual and combined effects of verbal suggestion and imagery on pain, itch, and fatigue as indicators of physical sensitivity in a randomized study design. Healthy participants (n = 116) were given an inert (placebo) capsule that was said to be effective for reducing physical sensitivity in either the majority (positive verbal suggestion) or the minority (control verbal suggestion) of users. Subsequently, they imagined either their best possible health (positive imagery) or a typical day (control imagery). Sensitivity to pain, itch, and fatigue was tested using a cold pressor test, histamine iontophoresis, and a bicycle test, respectively. Heart rate and skin conductance were recorded continuously. Results showed that positive verbal suggestion and imagery successfully induced positive expectations, but they did not affect physical sensitivity, as indicated by sensitivity to pain, itch, or fatigue, or concurrent physiological responses. These results could indicate that the specificity and concreteness of expectation inductions might be important for their applicability in the treatment of physical symptoms.

Trial Registration

Nederlands Trial Register NTR3641     

Significant Determinants of Mouse Pain Behaviour

Transgenic mouse behavioural analysis has furthered our understanding of the molecular and cellular mechanisms underlying damage sensing and pain. However, it is not unusual for conflicting data on the pain phenotypes of knockout mice to be generated by reputable groups. Here we focus on some technical aspects of measuring mouse pain behaviour that are often overlooked, which may help explain discrepancies in the pain literature. We examined touch perception using von Frey hairs and mechanical pain thresholds using the Randall-Selitto test. Thermal pain thresholds were measured using the Hargreaves apparatus and a thermal place preference test. Sodium channel Nav1.7 knockout mice show a mechanical deficit in the hairy skin, but not the paw, whilst shaving the abdominal hair abolished this phenotype. Nav1.7, Nav1.8 and Nav1.9 knockout mice show deficits in noxious mechanosensation in the tail, but not the paw. TRPA1 knockout mice, however, have a loss of noxious mechanosensation in the paw but not the tail. Studies of heat and cold sensitivity also show variability depending on the intensity of the stimulus. Deleting Nav1.7, Nav1.8 or Nav1.9 in Nav1.8-positive sensory neurons attenuates responses to slow noxious heat ramps, whilst responses to fast noxious heat ramps are only reduced when Nav1.7 is lost in large diameter sensory neurons. Deleting Nav1.7 from all sensory neurons attenuates responses to noxious cooling but not extreme cold. Finally, circadian rhythms dramatically influence behavioural outcome measures such as von Frey responses, which change by 80% over the day. These observations demonstrate that fully characterising the phenotype of a transgenic mouse strain requires a range of behavioural pain models. Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether.     

Nociceptive reactions during stimulation of immunity in rats with various individual resistance to stress

Various behavioural nociceptive reactions and individual resistance against stress were studied under conditions of stimulation of the immune processes by various techniques. The research problems included a study of influence of the immune stimulation with preparation "Imunofan" upon pain responses depending on individual resistance of animals to a stress, and the obtained results were compared with similar data in natural model of immune activation. To reveal central immune regulation of nociceptive reactions, imunofan was injected into brain ventricles. The work was carried out in 43 "Wistar" adult male rats. Free "open field" behaviour of animals was recorded to define a stress-resistance. Following nociceptive reactions, tail-flick to thermal stimuli; start, escape, jumping and vocalization to electrical skin stimulation, were studied. It was shown that intramuscular injection of imunofan (0.01 ml, 0.005% solution) depressed an active behaviour of animals in open field and reduced pain thresholds. This hyperalgesia was much higher in non-resistant rats in comparison to the resistant ones. Similar results were obtained in natural activation of immunity caused by operative procedure necessary for injection of imunofan into ventricles. Intracerebroventricular injections were accompanied by stronger and more complex changes of pain sensitivity.     

Involvement of the pineal gland and melatonin in murine analgesia

The data presented herein suggest that an intact pineal gland is required for the expression of the increased nocturnal sensitivity to morphine observed in mice. We report that the day/night rhythm of morphine analgesia was not evident in pinealectomized mice. Further, mice treated with melatonin exhibited a dose-related analgesic response. The decrease in sensitivity to pain was not observed in animals in which melatonin administration was followed by the opiate antagonist, naloxone. These data suggest that information derived from environmental lighting regulates sensitivity to pain via the pineal gland hormone melatonin, which is released and acts upon other areas of the CNS.     

The recovery of sensory function following skin flaps in humans

Two cross-sectional studies were made of the recovery of tactile and pain sensitivity in subjects having skin flaps in the region of the chest and neck as a result of tumor excision. In experiment 1, stimuli ranging from 2.46 to 17.10 gm of force were delivered by von Frey hairs to the flaps and comparable normal sites in 35 subjects at times ranging from 1 month to 10 years after surgery. No subjects perceived stimuli of less than 11.80 gm, thermal, or moving touch applied to flaps, whereas 21 percent perceived 11.80 gm or greater force (judged as painful applied to normal skin). The results of experiment 2 showed that these findings were not due to visual information available to subjects. Possible explanations for the fact that these results are radically different from those reported in the literature are discussed.     

Use of local anaesthesia for pain management during husbandry procedures in Australian sheep flocks

Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-knotching are routine husbandry procedures conducted on many millions of lambs annually in Australia, causing considerable pain and suffering. However, establishing an effective alternative to mulesing is proving to be a difficult and prolonged process. This is particularly so for producers of high-quality fine wool from Merino sheep that have been selected over many generations for skin wrinkle to increase yields, increasing their susceptibility to flystrike by Lucilia cuprina. In late 2005, a spray-on product formulation containing two topical analgesia agents (lignocaine and bupivacaine) for pain relief at mulesing has become commercially available. Increasingly, fine-wool growers have been choosing to continue surgical mulesing, but adopting pain alleviation at surgical mulesing to reduce suffering. This product has led to the development of the “Better Choices” program, in an effort to meet international concerns that mulesing without pain relief was cruel. Studies have been conducted on the use of these products for decrease of pain induced by surgical mulesing, castration and tail-docking. A technique has been developed to measure pain through assessment of wound sensitivity using Von-Frey Hair stimulation, measuring local involuntary reflexes and central cognition. These responses were graded using a numerical rating scale. Behavioural responses to pain were analysed by video. A novel technique was developed to assess the rate of wound healing by digital photography and computerized surface area measurement. Also, a method of application was developed at castration, which enabled analgesia of the remaining scrotal contents, with impressive results compared to other methods of castration such as the use of rubber rings. Findings from a series of field and pen trials indicate that the immediate application of spray-on topical anaesthesia to mulesing, castration and tail-docking wounds, significantly reduced the pain experienced post-procedure and improved the rate of wound healing. Increasing adoption by producers of pain relief for lambs during surgical routine husbandry procedures offers a new welfare-conscious paradigm for the Australian wool industry. This development has potential application to several species undergoing many livestock procedures throughout the world and offers a simple part solution to address the increasingly important and emerging global issue of welfare conscious agriculture.