Consciousness was once a topic that mainstream scientists would not address. In recent years, however, the study of consciousness has attracted a multidisciplinary following that includes neuroscientists, behavioral scientists, evolutionary biologists, computer scientists, mathematicians, physicists, and philosophers [l–3]. Consciousness researchers pursue the question of how the physical brain can produce phenomenal reality, how the brain organizes a coherent awareness from the chaos of sensory input, the sense of self, the mechanisms of blind sight and blind touch, and myriad other phenomena of awareness. Among the questions that consciousness researchers must ask are “What is the nature of pain? Why do we have the ability of feel pain? Why does pain hurt?”
Erroneous beliefs prevent effective management of infant pain, with the focus on self-report of the current definition of pain leading to neglect of nonverbal diagnostic information. Models of pain should consider not only experience but pain expression and how this is decoded and interpreted. The commonsense appeal of the belief that pain is a conscious experience is deficient, because there is no consensus on the nature of consciousness. Caregivers tend to self-reference and search for adult capacities for focal awareness in infants. The search seems to obfuscate our understanding of infant pain. Greater attention should be devoted to age-specific experience, the emotional distress of pain in infancy, and the important role of implicit information processing, or an impact for pain outside of focal attention.
Interstitial cystitis is a visceral pain syndrome whose incidence and severity have long been underestimated. Classifying it as a “complex visceral pain syndrome” rather than as a “disease of the bladder” is justified based on evidence that the driving process behind this illness is neurogenic inflammation, which is often not restricted to the bladder. This reclassification should help us understand that many of the current urologic therapies for interstitial cystitis can cause a worsening of the syndrome and should lead practitioners to offer rational pain-relieving treatments to their patients early on in the course of their illness.
This collective review of relevant research literature was to better understand the influence of cultural experience upon chronic pain perception. Using a structured review guideline, literature search was guided by a search strategy, quality grading of studies, data extraction and thematic, tabulated analysis of data. Themes were identified in three levels (1) patient, (2) the patient-provider interaction and (3) healthcare system. Clinical practice implications of the study included improving clinician cultural awareness, improving clinician cultural competency, culturally relevant pain measures and developing culturally-equitable systems of care. Research implications were the need for appropriate research based in a research agenda that brings the learnings of existing research to bear upon local contexts to enhance patient care.
The mu(3) opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (eg, morphine) and opioid peptide (eg, methionine enkephalin) insensitive. The binding is monophasic, saturable, and stereospecific, as well as naloxone reversible. This opiate receptor subtype has been found on human and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune downregulating activities parallels those actions formerly attributed to nitric oxide. Thus, this opiate receptor represents an addition to mu receptor heterogeneity that offers an explanation for the difference in actions of opioid peptides and opiate alkaloids in physiological systems transcending analgesia.
This Commentary evaluates several observations and hypotheses made by Fundytus and Coderre: (1) Initial treatment with high doses of μ-opioid agonists decrease phosphatidlylinositol (PI) hydrolysis, while (2) chronic treatment increases PI hydrolysis to near control levels via increased activity of type I metabotropic glutamate receptors (mGluRs) and/or δ-opioid receptors. (3) The resulting inositol 1,4,5-trisphosphate-mediated increase in protein kinase C then phosphorylates a μ-opioid coupled G-protein, leading to a desensitization of μ-opioid receptors; phosphorylates N-methyl-D-aspartate (NMDA) receptor-associated Ca2+ channels, resulting in a release of these channels from an Mg2+ block; and increases Ca2+/calmodulin-dependent protein kinase, which produces additional phosphorylation of μ-opioid coupled G-protein, leading to further desensitization of μ-opioid receptors. (4) A role for type II/III mGluRs in opioid dependence occurs from desensitization of these receptors, which allows 3′,5′-cyclic adenosine monophosphate to remain at levels high enough to produce withdrawal symptoms. (5) Second messenger systems interact. We then review some of the observations with which a model of opioid tolerance should be consistent. Finally, we review a model for opioid tolerance that we recently proposed.
Geissen Robinson, and Riley present a stimulating conceptual model of coping with chronic pain in which the authors argue that maladaptive beliefs and coping are primary determinants of adjustment and influence adaptive beliefs and coping through their influence on perceptions of control. We discuss some aspects of the model that require further refinement. First, the assessments of beliefs, appraisals, and coping need to be independent of outcome, obviating the use of “adaptive” and “maladaptive” in conceptual models. Unqualified statements about the universal adaptiveness, or maladaptiveness, of appraisal and coping strategies are likely to be unusual, since some strategies may result in higher emotional adjustment but not physical adjustment or vice versa. Second, beliefs, appraisals, and coping are distinct conceptual dimensions. Conceptual models that delineate relevant dimensions of these constructs rather than unify these partially independent constructs will likely have greater utility. Third, broadening the conceptualization of pain appraisal to include the individual's interpretation of the meaning of the pain is likely to provide expanded understanding of the pain coping process. Fourth, factors active in the individual's environment, particularly social relationships, need to be integrated into any comprehensive model of coping with chronic pain. And fifth, the bidirectional relationships between beliefs, appraisals, and coping need to be integrated into conceptual models. These processes are interrelated and feed back to one another as the individual struggles to cope with the challenges and threat posed by pain. The inherent complexity of coping with pain requires conceptualizations that address its transactional nature and methodologies that capture this dynamic process. Our comments direct future investigators to address when coping works, in what way it works, and for whom it works.
The main κ opioid receptors (κORs) subtypes already described (κ1ORs and κ2ORs) are expressed in brain regions involved in aversive memory consolidation, including the dorsal hippocampus (DH). However, the role of DH κORs in consolidation of aversive memories with varied intensity and specificity is still uncertain. The present study aimed to investigate this question using pharmacological agents in rats subjected to a weak, moderate or strong contextual aversive conditioning (CAC) protocol. Antagonizing DH κORs with nor-binaltorphimine (nor-BNI), immediately after, but not 6 h later, a moderate CAC leads to intensified freezing behavior in the re-exposure to the paired context. Thus, indicating that DH κORs have an inhibitory role in the consolidation of an aversive memory. Increased DH κORs expression 1 h and 3 h after the moderate CAC was also observed. This up-regulation was absent in animals only exposed to the shock or to the context, indicating that this phenomenon requires a shock-context pairing to occur. Intra-DH nor-BNI infusion induced no changes following a weak CAC, but it was able to potentiate the expression of freezing behavior in novel and unpaired context after a strong CAC, indicating that DH κORs also modulate the consolidation of a more intense and generalized memory. Moreover, infusing the κ2ORs agonist GR 89696, but not the κ1ORs agonist U-69593, into the DH reduced the conditioned freezing expression. Nor-BNI pretreatment in a sub-effective dose prevented the κ2ORs agonist effects. Altogether, the present findings provide convergent evidence that κORs activation negatively modulates contextual aversive memory consolidation in rat dorsal hippocampus.
This Commentary addresses some common conceptual errors and methodological issues raised by the Focus article by Geisser, Robinson, and Riley. One conceptual error, the problem of confounding coping with outcome, is evident in their assertion that catastrophizing is not a form of coping, but rather a maladaptive pain belief. Catastrophizing clearly fits current definitions of coping, even though it may be associated with negative outcomes. A second conceptual error is the tendency to oversimplify the coping process that is evident in the tendency to divide coping strategies into dichotomous categories leg, active vs passive, adaptive vs maladaptive. Methodological issues raised by this article include: (1) the need to recognize the strengths of existing pain coping instruments (eg, the Coping Strategies Questionnaire), and (2) the utility of new and alternative coping measures. This Commentary concludes with a discussion of important directions for future research on pain coping.
Opioids represent one of the most commonly prescribed classes of drugs used to treat acute clinical pain. There are several biologic factors that influence the potency and efficacy of opioids. Until recently, it has been assumed that one's sex has little effect on the analgesic properties of these agents. Miaskowski and Levine's review of the literature and the original research findings by Gear and coworkers cast doubt on this assumption. They provide indirect evidence that females require less of a mu-opioid receptor agonist than males for the treatment of acute clinical pain. They provide more direct experimental evidence that females show a longer duration of analgesia in response to kappa-opioids compared with males. These findings are intriguing and are of both therapeutic and theoretical importance.
I agree with Bernard Rollin (in “Some Conceptual and Ethical Concerns About Current Views of Pain”) that it is implausible to hold that linguistic competence is a necessary condition for consciousness of pain. However, Rollin is incorrect to characterize this criterion as insulated from empirical disproof, because the best current theories of phenomenal consciousness that would support the criterion are themselves open to empirical disproof. Although I agree with Rollin that it would be implausible to deny that any nonhuman animals can feel pain, when we look closely at the relevant behavioral and neurophysiological evidence, we see that a good case can be made for saying that invertebrates (with the possible exception of cephalopods) probably cannot feel pain.
Recent evidence suggests that one of the factors that may influence the assessment and management of pain is a person's gender. However, only a limited amount of information exists on gender differences in responses to analgesic medications. Based on a review of the available literature published between 1966 and 1998, we suggest that opioids are better analgesics for women. The information in this paper comes predominantly from several studies on the use of patient-controlled analgesia for the management of postoperative pain. Additional information comes from our recent work that demonstrated a sexual dimorphism in oral surgery patients' responses to three different opioid analgesics that share the property of acting as agonists at the kappa-opioid receptor. The paper concludes with a discussion of the major recommendations for future research regarding the gender biology of pain.
The current definition of pain adopted by the International Association for the Study of Pain (IASP) and the American Pain Society (APS) chapter of the IASP is unacceptable because its claims and consequences are inconsistent with the IASP's stated purpose. The definition's apparent claims that (1) only effective communication of pain brings pain into existence, and that (2) researchers and clinicians are merely objective evaluators of whether such communication has occurred are inconsistent with the IASP's purpose to improve care of patients with acute and chronic pain through attention to patients, to the relationship between them and their caregivers, and to social policy. The definition's success at rejecting the consequences of Cartesian dualism is only partial. The definition contributes to a lack of justice for nonverbal patients.
The "modern" criterion of 50% pain relief has longstanding precedents in the "ancient" literature. We agree that other measures of outcome, which reflect pain relief indirectly, are important, and accordingly for over two decades have routinely reported activities of daily living, return to work, patient satisfaction, need for additional treatment, and medication requirements. Physician and patient may deceive themselves (L. fallax, deceit) by undue reliance on any single outcome criterion. Relief of pain per se, however, is most relevant to the patient's presenting complaint, and however we choose to quantitate it, it is a sine qua non.
