Comparative biology of pain: What invertebrates can tell us about how nociception works

Abstract

The inability to adequately treat chronic pain is a worldwide health care crisis. Pain has both an emotional and a sensory component, and this latter component, nociception, refers specifically to the detection of damaging or potentially damaging stimuli. Nociception represents a critical interaction between an animal and its environment and exhibits considerable evolutionary conservation across species. Using comparative approaches to understand the basic biology of nociception could promote the development of novel therapeutic strategies to treat pain, and studies of nociception in invertebrates can provide especially useful insights toward this goal. Both vertebrates and invertebrates exhibit segregated sensory pathways for nociceptive and nonnociceptive information, injury-induced sensitization to nociceptive and nonnociceptive stimuli, and even similar antinociceptive modulatory processes. In a number of invertebrate species, the central nervous system is understood in considerable detail, and it is often possible to record from and/or manipulate single identifiable neurons through either molecular genetic or physiological approaches. Invertebrates also provide an opportunity to study nociception in an ethologically relevant context that can provide novel insights into the nature of how injury-inducing stimuli produce persistent changes in behavior. Despite these advantages, invertebrates have been underutilized in nociception research. In this review, findings from invertebrate nociception studies are summarized, and proposals for how research using invertebrates can address questions about the fundamental mechanisms of nociception are presented.

Comparative Physiology of Nociception and Pain

“…Electrophysiological properties of nociceptors are discussed below (reviewed in Refs. 16,32,136); however, their main two functions are first to encode information on the modality of stimulus, intensity, and duration to reflex centers in the CNS, and second to underpin nocifensive withdrawal reactions (45) and mediate longer-term behavioral modifications by their continued excitation via pain mechanisms (133).…”

“…Many molecules and their receptors have been linked to nociception and pain, for example, acidsensing ion channels (ASICs) that mediate acid nociception and have been reviewed extensively elsewhere (16,73,103,136). Only two shall be highlighted here: transient receptor potential (TRP) channels heavily involved in thermal nociception, and opioid receptors and endogenous substances intrinsic to opioid-mediated analgesia.…”

“…Studying a variety of animal species affords us the opportunity to explore the evolution of nociception and pain. Taxonomic differences linked to life history, ecology, and evolutionary pressures can help inform why differences in the nociceptive system exist (16,129,136). By exploring empirical evidence from neuroanatomy, electrophysiology, and molecular biology, this review will discuss the differences and similarities that diverse animal groups share with mammals and provide possible explanations linked to animal physiology, lifestyle, and dangers in the environment.…”

The interruptive effect of electric shock on odor response requires mushroom bodies in Drosophila melanogaster

“…Studies with experimental animal have shed insight into the neural and molecular mechanisms of nociception. Drosophila melanogaster avoids nociceptive stimuli, jumps on noxious hot plate, cripples after being foot shocked and its nociception detecting system resembles vertebrate nociceptors anatomically and functionally . Flies are not just reflex upon nociceptive stimuli, they can form aversive memory by associating the conditioned stimulus (CS) with the nociceptive stimuli (US) .…”

“…avoids nociceptive stimuli, jumps on noxious hot plate, cripples after being foot shocked and its nociception detecting system resembles vertebrate nociceptors anatomically and functionally. 7,9,10,12,13,52,53 Flies are not just reflex upon nociceptive stimuli, they can form aversive memory by associating the conditioned stimulus (CS) with the nociceptive stimuli (US). [10][11][12] With a so-called "pain-relief paradigm", flies can even learn that a CS odor predicts the relief of "painful" US and thus prefer the CS.…”