Shackling of commercial poultry involves the insertion of each leg into parallel metal slots and holding the bird inverted for a period of time before stunning and slaughter. Nociceptors signalling noxious stimulation of the skin have been identified in the beak and feathered skin but not in the scaly skin of the leg. The physiological properties of the C-fibre mechanothermal (CMT) nociceptors in the skin over the tarsometatarsus in the lower leg were studied in response to quantitative mechanical stimulation. The electrical activity was recorded from single C-fibres dissected from the parafibular nerve in anaesthetized animals. The receptive fields of these receptors were small and spot-like, measuring in the region of 1-3 mm in diameter. The threshold to mechanical stimuli ranged from 0.8-15 g using von Frey filaments, and from 3-33 g using a 0.5mm probe mounted on a feedback-controlled stimulator. Stimulus response curves using a ramp-and-hold stimulus were recorded for a number of fibres. After comparing these threshold measurements and the stimulus response data with previous measurements of the force applied to the legs during shackling, it was concluded that shackling is likely to be a very painful procedure.

For the detection and assessment of pain in animals both behavioural and physiological measurements are necessary. Cutaneous receptors which responded to noxious stimulation (nociceptors) have been identified in birds and have been characterized physiologically in the chicken. Following cutaneous nociceptive stimulation the chicken showed cardiovascular and characteristic behavioural changes consistent with those seen in mammals and indicative of pain perception. Following major burn trauma (partial beak amputation) there was behavioural and electrophysiological evidence fora pain-free period lasting several hours. This pain-free period was followed by pain-related behaviour with both anatomical and physiological evidence for long-term chronic pain.

While pain has been assessed following nociceptive stimulation and following trauma the painful consequences of chronic disease have not been investigated Spontaneous degenerative joint disease is widespread in certain strains of intensively reared poultry, and while we do not know what effect joint degeneration has on the joint capsule receptors, recent work has shown in the joint capsule of birds there are similar receptor types to those found in mammals and it seems likely that joint degeneration in birds may be accompanied by painful sensations.

Experimental work has clearly detected painful conditions in birds but the alleviation of pain with analgesic drugs is not possible at present because analgesic agents have not been systematically investigated in birds.

Comparing pain in birds with mammals it is clear that, with regard to the anatomical, physiological and behavioural parameters measured, there are no major differences and therefore the ethical considerations normally afforded to mammals should be extended to birds.

Vast numbers of decapods are used in human food and currently subject to extreme treatments and there is concern that they might experience pain. If pain is indicated then a positive change in the care afforded to this group has the potential to produce a major advance in animal welfare. However, it is difficult to determine pain in animals. The vast majority of animal phyla have a nociceptive ability that enables them to detect potential or actual tissue damage and move away by a reflex response. In these cases there is no need to assume an unpleasant feeling that we call pain. However, various criteria have been proposed that might indicate pain rather than simple nociception. Here, with respect to decapod crustaceans, four such criteria are discussed: avoidance learning, physiological responses, protective motor reactions and motivational trade-offs. The evidence from various experiments indicates that all four criteria are fulfilled and the data are thus consistent with the idea of pain. The responses cannot be explained by nociception alone but, it is still difficult to state categorically that pain is experienced by decapods. However, the evidence is as strong for this group as it is for fish but the idea that fish experience pain has broader acceptance than does the idea of decapod pain. A taxonomic bias is evident in the evaluation of experimental data.

Small laboratory animals are commonly euthanased via intraperitoneal (IP) injection of sodium pentobarbital. However, there is concern that animals may experience pain prior to loss of consciousness with this delivery route. The present study investigated electroencephalographic (EEG) nociceptive responses of anaesthetised pigs to IP sodium pentobarbital injection using an established minimal anaesthesia model. Thirty commercial white line entire male pigs aged 10-15 days were minimally anaesthetised with halothane in oxygen. Following 10 min of baseline EEG data collection, pigs had their tails docked using side-cutters and, after a further 5-min interval, were euthanased via IP injection of sodium pentobarbital (250 mg kg-1). The summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were derived from the EEG data. For each variable in each pig, means were calculated for the following 60-s periods: immediately prior to tail-docking (baseline 1); immediately prior to pentobarbital injection (at least 4 min after docking; baseline 2); and for two consecutive 60-s periods immediately following pentobarbital injection (P1 and P2). Statistical analyses revealed no differences between the two baseline periods, indicating that transient EEG changes induced by tail-docking had resolved prior to pentobarbital injection. IP pentobarbital injection induced a significant increase in F50 and decrease in PTOT of the EEG during P1. This response is characteristic of acute nociception, indicating that conscious pigs likely perceive IP sodium pentobarbital as painful in the period prior to loss of consciousness.

This study examined electroencephalographic (EEG) indices of acute nociception in pigs (Sus scrofa) aged 1, 5, 7, 10, 12 and 15 days, post-natal. Ten pigs per age were anaesthetised with halothane in oxygen and maintained at a light plane of anaesthesia. EEG was recorded bilaterally using a five-electrode montage. Following a 10-min baseline period, tails were docked using side-cutter pliers and recording continued for a further 5 min. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) of the EEG were used to assess nociception. Tail-docking at one day of age induced no significant changes in the EEG spectrum. A typical nociceptive response, characterised by an increase in F50 and decrease in PTOT was evident at ten days of age, with five and seven day old pigs exhibiting responses in either F50 or PTOT only. Pooling of data into ≤ 7 days of age and > 7 days of age revealed F50 was higher overall in the older group. Whilst PTOT decreased after docking in both groups, this response was larger and more prolonged in the older group. F95 increased after docking in the older pigs only. Overall, these data provide evidence of an increase in cortical responsiveness to noxious stimulation with increasing post-natal age, suggesting there may be qualitative differences in pain perception between age groups. Further, the data provide some support for current recommendations that tail-docking and other painful husbandry procedures be performed within seven days of birth in order to minimise their impact on animal welfare.

Stress can exert modulatory effects on pain perception in animals, as exposure to a stressor can result in either the reduction or amplification of the perceived severity of pain. These phenomena are widely described as stress-induced analgesia (SIA) and stress-induced hyperalgesia (SIH). The two are mediated by the same underlying mechanisms, but occur due to different stressors and different responses from the pain pathway. SIA and SIH have been demonstrated with a variety of stress and pain stimuli in rodents, humans and other mammals. There is some evidence that SIA occurs in birds and that they have the neurological systems and brain regions necessary for SIH. Tonic immobility (TI) is related to SIA in mammals, and there is evidence the avian brain is compatible with TI having analgesic effect, but it could have a hyperalgesic effect. This review looks at the mechanisms and evidence of SIA, SIH and TI in mammals and discusses evidence relating to the occurrence of these phenomena in birds.

The peripheral nervous system (PNS) has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the “autonomic nervous system” (ANS), but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as “visceral” and “somatic” are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as “small dark” neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system.

The role of adenosine-5′-triphosphate (ATP) and of the ligand-gated P2X3 receptor in neuronal dorsal root ganglia (DRG) pain transmission is relatively well established. Much less is known about the purinergic system in trigeminal ganglia (TG), which are involved in certain types of untreatable neuropathic and inflammatory pain, as well as in migraine. Emerging data suggest that purinergic metabotropic P2Y receptors on both neurons and satellite glial cells (SGCs) may also participate in both physiological and pathological pain development. Here, we provide an updated literature review on the role of purinergic signaling in sensory ganglia, with special emphasis on P2Y receptors on SGCs. We also provide new original data showing a time-dependent downregulation of P2Y2 and P2Y4 receptor expression and function in purified SGCs cultures from TG, in comparison with primary mixed neuron–SGCs cultures. These data highlight the importance of the neuron–glia cross-talk in determining the SGCs phenotype. Finally, we show that, in mixed TG cultures, both adenine and guanosine induce intracellular calcium transients in neurons but not in SGCs, suggesting that also these purinergic-related molecules can participate in pain signaling. These findings may have relevant implications for the development of new therapeutic strategies for chronic pain treatment.

Satellite glial cells (SGCs) undergo phenotypic changes and divide the following injury into a peripheral nerve. Nerve injury, also elicits an immune response and several antigen-presenting cells are found in close proximity to SGCs. Silencing SCG-specific molecules involved in intercellular transport (Connexin 43) or glutamate recycling (glutamine synthase) can dramatically alter nociceptive responses of normal and nerve-injured rats. Transducing SGCs with glutamic acid decarboxylase can produce analgesia in models of trigeminal pain. Taken together these data suggest that SGCs may play a role in the genesis or maintenance of pain and open a range of new possibilities for curing neuropathic pain.

Activation of cyclic AMP response element-binding protein (CREB) in the spinal dorsal horn may be a crucial contributor to the activity-dependent synaptic plasticity that is thought to underlie the development of persistent pain following peripheral nerve injury. In this study, we examined the early period of CREB activation following chronic constriction injury (loose ligation) of the sciatic nerve in rats. The estimated levels of Ser133-phosphorylated (activated) CREB significantly increased at 2 hours (424 ± 85%) and remained elevated at 4 hours (349 ± 97%) and 8 hours (258 ± 69%) after sciatic ligation compared with control animals. By contrast, activated CREB levels in sham-operated animals were not significantly greater than in control animals except at 1 hour (176 ± 6%) and 8 hours (288 ± 16%). The maximal ligation-associated activation of CREB at 2 hours occurred bilaterally and was dependent, at least partly, on NMDA-receptor activation because pretreatment with 20 µg MK-801 significantly attenuated the ligation-associated activation of CREB. The levels of non-phosphorylated CREB in ligated and sham-operated animals did not differ significantly from controls at the time-points examined.

These data establish a significant, persistent increase in CREB phosphorylation within hours of loose ligation of the sciatic nerve and indicate an early but consequential injury-related shift in the manner in which spinal dorsal horn neurons processed sensory information. The data lend further support to the notion that ligation-associated CREB-dependent synaptic plasticity in the spinal dorsal horn might underlie the development of persistent pain following peripheral nerve injury.

Light microscopic observations employing intravital methylene blue staining and impregnation by the zinc iodide-osmium tetroxide technique are presented for intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat snout. Both procedures revealed anatomical details of the intraepidermal nerve fibre plexus in epidermal hillocks often located very close to the mouths of hairs. These nerve fibres appeared to resemble those described in previous immunohistochemical studies as cluster or bush endings. The methylene blue preparations demonstrated the existence of an intensely stained enlargement at the site of the branching point of the nerve fibres which seemed to be functionally related to the development of such nerve fibre plexuses. Due to their close association with hairs, these nerve fibre plexuses are most likely to be mechanoreceptive. Additionally, solitary varicose nerve fibres were found loosely distributed within the epidermis. The visualisation of 2 different morphological types of nerve fibre endings extends the validity of the concept of punctate sensibility into the epidermis. Methylene blue staining appeared to be somewhat superior to the zinc iodide-osmium tetroxide technique. Due to their selectivity for intraepidermal nerve fibres, the methods applied here supplement immunohistochemical procedures in a helpful manner.

The spinal mechanisms of action of opioids under normal conditions are reasonably well understood. The spinal effects of opioids can be enhanced or reduced depending on pathology and activity in other segmental and nonsegmental pathways. This plasticity will be considered in relation to the control of different pain states using opioids. The complex and contradictory findings on the supraspinal actions of opioids are explicable in terms of heterogeneous descending pathways to different spinal targets using multiple transmitters and receptors – therefore opioids can both increase and decrease activity in descending pathways. These pathways could exhibit considerable plasticity. There is increasing evidence that delta opioid receptor agonists have the potential to replace morphine as major analgesics with reduced side-effect profiles. The concept of preemptive analgesia, based on preventing the induction of some of the negative plastic influences on opioid controls and the detrimental effects of pain, is sound, but experimental verification in the clinical setting is difficult. For example, a delayed compensatory upregulation of inhibitory systems, particularly in inflammation, may counter persistent painful inputs. Combination therapy with opioids may be beneficial in many pain states where either negative influences are blocked or inhibitory controls are enhanced. Finally, developmental aspects of these systems are discussed in connection with the treatment of pain in young children, where inhibitory systems in the spinal cord are immature.

This target article examines the clinical and experimental evidence for a role of peripheral and central hyperexcitability in persistent pain in four key areas: cutaneous hyperalgesia, referred pain, neuropathic pain, and postoperative pain. Each suggests that persistent pain depends not only on central sensitization, but also on inputs from damaged peripheral tissue. It is instructive to think of central sensitization as comprised of both an initial central sensitization and an ongoing central sensitization driven by inputs from peripheral sources. Each of these factors, initial sensitization, ongoing central sensitization, and inputs from peripheral sources, contributes to the net activity in dorsal horn neurons and thus influences the expression of persistent pain or hyperalgesia. Since each factor, peripheral inputs and central sensitization (initial or ongoing), can contribute to both the initiation and maintenance of persistent pain, therapies should target both peripheral and central sources of pathology.

There are some conspicuous differences between the sensibilities of cutaneous and visceral tissues: (1) Direct trauma, which readily produces pain when applied to the skin, is mostly without effect in healthy visceral tissue. (2) Pain that arises from visceral tissues is initially often poorly localised and diffuse. (3) With time, visceral pains are often referred to more superficial structures. (4) The site of referred pain may also show hyperalgesia. (5) In disease states, the afflicted viscera may also become hyperalgesic. In this target article, I consider to what extent differences in the physiology, anatomy, and chemistry of peripheral processing systems explain these different sensibilities. In almost every aspect, there are subtle differences in the properties of the processing mechanisms for cutaneous and visceral information. These may arise because of distinct developmental cues operating in the two domains. Many of the differences between visceral and cutaneous afferents are quantitative rather than qualitative. The quantitative differences, for example in the density of afferent innervation, can be large. The quantitative differences in the numbers of afferents alone may be a sufficient explanation for some aspects of the differential sensibility, for example, the poor localisation of sensation and the apparent insensitivity to focal yet tissue- damaging stimuli. In addition, the few clear qualitative differences apparent in the innervations of the two tissue types may be of special importance. That the encoding of visceral nociceptive events may occur by an intensity mechanism rather than a specificity mechanism could be the key difference in viscerosensory and somatosensory processing.