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PubMedDate not supplied

Nociceptors and the peripheral nervous system's role in pain.

This article reviews the role that the peripheral nervous system plays in pain perception. The first section describes the functional properties of the primary sensory element-the nociceptor-and how its behavior is related to pain perception. The second section describes the current state of knowledge concerning the way our nociceptive sensing system changes as a result of tissue injury, including those changes related to sympathetic nervous system modulation of pain.

Humans↗

PubMed1993

[The problems of quantifying pain in animals].

A classification of vertebrates concerning their pain sensibility from the anatomical or physiological point of view is made very difficult by the different pathways of nociception. The very good measurable stimuli are answered by a wide range of reactions. In search for approved parameters for the characterization of pain objectivity is often preferred to validity. Studies using animals in painful situations with and without analgetic treatment are considered favourable for pain evaluation. Each kind of evaluation of pain in animals has to take into account the different dimensions of pain perception. As a result we would like to follow Kitchell's statement (1980), as a guideline for the work with animals: "Overemphasis on the uncertainty of knowledge about pain in animals that leads to a denial that pain perception exists in animals is logically as well as empirically unfounded."

Animals↗

PubMed2005

High and low unstimulated salivary cortisol levels correspond to different symptoms of functional gastrointestinal disorders.

OBJECTIVE: It was examined whether unstimulated salivary cortisol levels as a psychobiological marker of stress reactivity correspond to psychological assessments of pain perception, depressive mood, and anxiety in patients with functional gastrointestinal disorder (FGD). METHODS: A total of 30 patients was diagnosed according to the Rome diagnostic criteria for irritable bowel syndrome, nonulcer dyspepsia, or both conditions. Psychometric data were assessed by questionnaires, and salivary samples were collected for the measurement of cortisol levels after awakening and during the day. Patients were grouped by their awakening cortisol levels into low (G1), medium (G2), and high cortisol group (G3). RESULTS: Psychiatric comorbidity did not differ between the groups. Analysis of variance (ANOVA) showed significant group differences with respect to pain perception and depressive mood, with the highest pain in G1 and the highest depression in G3. CONCLUSION: The reported results are in line with prior research on hypothalamus-pituitary-adrenal (HPA) axis dysregulation in patients suffering from somatoform disorders on the one hand (low cortisol levels) and high cortisol levels in depression on the other. It is remarkable that our sample of patients of whom all received the same diagnosis, i.e., FGD, can be subdivided according to functional gastrointestinal symptoms, which correspond to the two types of cortisol alterations. The data provide evidence for psychobiological subgroups in FGD patients. As a consequence, the predominant symptoms reported by patients with FGD should carefully be taken into account to specify (psychotherapeutic) treatment.

Adult↗

PubMed2004

Femoral nerve block for total knee arthroplasty patients: a method to control postoperative pain.

This study was designed to determine the effects of a single-injection femoral nerve block (FNB) using 30 mL of 0.5% bupivacaine with epinephrine 1:200,000, on pain control following total knee arthroplasty (TKA). Forty patients were randomly distributed into 2 groups: Group A received general anesthesia plus a FNB (n = 19), whereas Group B received general anesthesia plus a FNB with 30 mL of preservative-free saline (n = 21). The amount of morphine used, sedation, and average pain perception were measured for the first 24 hours and daily postoperatively. Group A used significantly less morphine (48.1 mg) compared with Group B, which used 76.2 mg during the first 24 hours after surgery (P = 0.003). Group A's sedation scale was significantly less than group B's (2.26 vs 2.67) (P = 0.045). The average pain perception was significantly different (P =.002). Postoperative management of pain following TKA can be improved through a preoperative single-injection FNB with 0.5% bupivacaine plus epinephrine 1:200,000. The cost is minimal, risks appear acceptable, and the procedure is efficacious.

Aged↗

PubMed1998

Desensitization of bladder sensory fibers by intravesical capsaicin or capsaicin analogs. A new strategy for treatment of urge incontinence in patients with spinal detrusor hyperreflexia or bladder hypersensitivity disorders.

Recent experimental studies have identified a category of unmyelinated type C bladder afferent fibers in the pelvic nerves which are extremely sensitive to capsaicin. Sensory input conveyed by these fibers triggers a spinal reflex which, in chronic spinalized animals, facilitates and controls micturition. In addition, bladder C fibers were also shown to have a role in bladder pain perception. In humans capsaicin-sensitive afferent fibers also innervate the bladder and contribute to the reflexogenic control of the detrusor muscle and to bladder pain perception. Desensitization of such fibers by intravesical administration of capsaicin, presumably by blocking sensory transmission, has been shown to reduce involuntary micturition and to increase bladder capacity in patients with detrusor hyperreflexia of spinal origin, and to reduce the intensity of bladder pain in patients with bladder hypersensitivity. Very recently, resiniferatoxin, an ultrapotent capsaicin analog, was shown to have a similar clinical effect in this subset of patients. However, unlike capsaicin, resiniferatoxin did not evoke acute irritative urinary symptoms during bladder instillation.

Administration, Intravesical↗

PubMed2002

Synthetic heat at mild temperatures.

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40 degrees C) and cool (> or = 27 degrees C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3 degrees C. Cooling by just 1 degrees C from a base temperature of 33 degrees C led to reports of heat on more than 1/3 of trials, and cooling by just 3 degrees C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29 degrees C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.

Adult↗

PubMed2004

Silent myocardial ischemia may be related to inflammatory response.

Silent myocardial ischemia (SMI) is a common phenomenon in patients with coronary artery diseases, which frequently occurs at rest, during daily life activities or after physical or emotional exertion. Although individual differences in pain threshold may partially explain the variability in pain perception, the mechanisms responsible for SMI are not well understood. A defective warning mechanism was proposed by some investigators as the reason for the absence of pain, stressing that sensibility to pain differs from patient to patient. A central nervous system as well as peripheral nerve endings alteration was also posited. There is increasing evidence that the development of atherosclerosis is associated with inflammation, and increased levels of inflammatory markers have been documented in various settings of coronary artery disease. Patients with chronic and stable coronary artery disease have clear evidence of a low-grade inflammation, which is independent of traditional cardiovascular risk factors. A systemic inflammatory response to coronary angioplasty has also been reported after balloon angioplasty and after stent implantation. More recently, intriguing observations have shown that there is a particular biochemical pattern of inflammatory system activation (an increased production of inflammatory cytokines) that explains the lack of anginal symptoms in patients with silent myocardial ischemia. That is, pain perception may result from microenviromental balance between proinflammatory and anti-inflammatory cytokines.

Angina Pectoris↗

PubMed2004

Fear-induced hypoalgesia in humans: effects on low intensity thermal stimulation and finger temperature.

UNLABELLED: Prior research indicates that exposure to fear-inducing stimuli inhibits finger withdrawal to sudden onset and high intensity radiant heat in humans. Although withdrawal latencies to intense heat are thought to reflect changes in spinal nociceptive processing, supraspinal measures are needed to determine whether pain perception is altered. The present study used gradual onset and low intensity radiant heat to induce a finger withdrawal response that depends on supraspinal processes. After baseline pain threshold tests, 57 healthy human participants were randomly assigned to 1 of 2 groups. In the fear group, participants received 3 brief shocks. In the neutral group, participants did not receive shock. Results suggest that finger withdrawal latencies to low intensity heat were increased after shock presentation, providing additional evidence that fear reduces pain on a measure that is influenced by supraspinal processes. Both self-report and physiological (skin conductance level, heart rate, and blood pressure) measures of emotion confirmed that the intended affective states were induced. Finger temperature was unaffected by emotion manipulations; thus, skin cooling does not appear to mediate increased withdrawal latencies. These findings provide additional evidence that fear not only inhibits spinal nociceptive reflexes, it also inhibits supraspinal measures of pain. PERSPECTIVE: From a clinical perspective, these data suggest that patients who experience intense fear in response to unpredictable threatening events will show a reduction in pain perception.

Adolescent↗

PubMed2001

Comparison of pain and time of procedures with two first-trimester abortion techniques performed by residents and faculty.

OBJECTIVES: We compared pain perception and procedure time in abortions performed by residents and faculty using a manual vacuum aspirator and electric vacuum curettage devices. STUDY DESIGN: We conducted a randomized trial of 114 women undergoing first-trimester abortions. Patients assessed the level of pain with visual analog scales. RESULTS: The mean procedure times were 5.7 and 6.9 minutes, respectively, with electric vacuum curettage and manual vacuum aspirator. Faculty took less time than residents to perform both procedures. Patients reported a higher pain level with cervical dilatation before resident electric vacuum curettage procedures. Patients undergoing electric vacuum curettage thought that the procedure noise increased their pain. CONCLUSIONS: First-trimester abortion procedures can be performed more quickly by experienced surgeons. The procedure time for the manual vacuum aspirator is greater than that for the electric vacuum curettage. Patient pain perception with aspiration by these two techniques is not different. The level of pain after aspiration did not vary significantly in patients who had abortions performed by residents or faculty.

Abortion, Induced↗

PubMed2005

Effect of the menstrual cycle on pain experience associated with periodontal therapy: randomized, pilot study.

OBJECTIVES: The aim of this pilot cross-over study was to compare preliminarily the pain perception of female patients undergoing periodontal debridement during menstrual or pre-menstrual phases (peri-menstrual period) with that observed during mid-menstrual phase (post-menstrual period). MATERIALS AND METHODS: Twenty women with moderate-to-advanced chronic periodontitis and regular menstrual cycles were asked to complete Corah's Dental Anxiety Scale (DAS) during the first debridement visit. Patients were randomly assigned to receive their first debridement visit during either their peri-menstrual or post-menstrual period. Debridement was performed in bilateral quadrants of patients during the periods. Pain levels for each quadrant were assessed with a Visual Analogue Scale (VAS), after each debridement visit. RESULTS: There was no significant correlation of order of treatment in the intensity of perceived pain during the periods (p<0.05). The median VAS scores were 22.0 and 15.2 mm in the peri-menstrual and the post-menstrual period, respectively. Increase in pain perception among females during their peri-menstrual period was significantly greater than their post-menstrual period (p<0.05). CONCLUSION: No clinical conclusions can be drawn at this stage as this pilot study did not have a sufficiently broad population to generalize these observations to all female periodontal patients. Providing clinicians with information about patients' menstrual cycle during debridement can alter the pain experience.

Adult↗

PubMed2002

The role of sex hormones on formalin-induced nociceptive responses.

Many chronic pain conditions are more frequent in women than in men. This observation suggests that there is a potential role of sex hormones on pain perception. In the present study, we measured nociceptive responses to the formalin test in normal and gonadectomized male and female rats. The nociceptive responses to formalin injection were divided in four phases: acute (phase I), interphase and late phases (phases II and III). Four groups of rats were tested: (a) males (n = 15), (b) females (n = 16), (c) ovariectomized females (OVX) (n = 15) and (d) castrated males (CAST) (n = 15). Females presented significantly more nociceptive responses than males during phase I, interphase and phase II (P < 0.01). They also presented significantly more nociceptive responses than OVX females during the interphase (P < 0.05). CAST males presented significantly more nociceptive responses during the phases I (P < 0.01), II (P < 0.01) and III (P < 0.05) than the male rats. Finally, the responses of CAST males and OVX females were virtually identical, suggesting that the differences recorded between males and females in the formalin test were related to an activational effect of the sex hormones rather than an organizational effect. In conclusion, these results permit the support of the role of sex hormones on the modulation of pain perception. Interestingly, male and female sex hormones seem to act specifically on the different phases of the formalin test, suggesting some specific roles for sex hormones in different pain conditions.

Animals↗

PubMed1987

Ethnicity and pain: a biocultural model.

Zborowski's pioneering research in the 1950s noted ethnic differences in pain response. Subsequent clinical research has focused on ethnic variability in psychological, attitudinal and behavioral response but generally has ignored sociocultural influences on the perceptual component of pain. In light of Melzack and Wall's gate-control theory, it now appears that sociocultural factors may affect the psychophysiological processes of pain perception. This paper proposes that a biocultural model, which combines basic social learning and social comparison theories with certain aspects of the gate-control theory, will prove useful for studying and understanding cultural influences on human pain perception and response.

Cultural Characteristics↗

PubMed1981

Behavioral medicine in hemophilia arthritic pain management: two case studies.

Hemophilia represents a congenital hereditary disorder of blood coagulation characterized by recurrent unpredictable bleeding episodes affecting any body part, especially the joints and extremities. Repeated hemarthrosis eventually results in degenerative arthritis accompanied by severe chronic pain. As contrast to acute bleeding pain, which serves as a functional signal, chronic arthritic pain is a debilitating condition often resulting in analgesic abuse and/or addiction. Two adult hemophiliacs with severe chronic arthritis received training in progressive muscle relaxation exercise, meditative breathing, and imagery associated with past experiences of pain reduction. Imagery training resulted in clinically significant reductions in arthritic pain perception for both patients, maintained over an 8-month follow-up period. Concomitant Measures also demonstrated significant therapeutic gains. Thermal biofeedback assessment of the arthritic joint provided a biophysiological measure of learned temperature control through the imagery techniques. The findings are discussed in relationship to medical observations on the therapeutic value of warming and heat application in the management of arthritic joints, as well as other potential mechanisms which might have contributed in the reduction of arthritic pain perception. Finally, the importance of differentiating between acute bleeding pain management and chronic arthritic pain is emphasized, as well as the necessity of the application of the techniques within an interdisciplinary team setting.

Adult↗

PubMed2005

Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness.

Visceral and somatic pain perception differs in several aspects: poor localization of visceral pain and the ability of visceral pain to be referred to somatic structures. The perception of pain intensity and affect in visceral and somatic pain syndromes is often different, with visceral pain reported as more unpleasant. To determine whether these behavioral differences are due to differences in the central processing of visceral and somatic pain, non-invasive imaging tools are required to examine the neural correlates of visceral and somatic events when the behavior has been isolated and matched for either unpleasantness or pain intensity. In this study we matched the unpleasantness of somatic and visceral sensations and imaged the neural representation of this perception using functional magnetic resonance imaging in 10 healthy right-handed subjects. Each subject received noxious thermal stimuli to the left foot and midline lower back and balloon distension of the rectum while being scanned. Stimuli were matched to the same unpleasantness rating, producing mild-moderate pain intensity for somatic stimuli but an intensity below the pain threshold for the visceral stimuli. Visceral stimuli induced deactivation of the perigenual cingulate bilaterally with a relatively greater activation of the right anterior insula-i.e. regions encoding affect. Somatic pain induced left dorso-lateral pre-frontal cortex and bilateral inferior parietal cortex activation i.e. regions encoding spatial orientation and assessing perceptual valence of the stimulus. We believe that the observed patterns of activation represent the differences in cortical process of interoceptive (visceral) and exteroceptive (somatic) stimuli when matched for unpleasantness.

Adult↗

PubMedDate not supplied

Post-traumatic stress, pain and anxiety in adult burn victims.

This article describes the relationship between post-traumatic morbidity, anxious anticipation of pain and pain perception in 33 adult burn patients. Burn patients were assessed, on average, 7 days after admission to the hospital. Five times a day nurses asked the patients to provide pain ratings. The more patients suffered from post-traumatic stress, the more their anxiety state was elevated. The association between post-traumatic stress and pain perception was, controlling for the effects of anxious anticipation, spurious.

Adolescent↗

PubMed2005

Specificity of female and male sex hormones on excitatory and inhibitory phases of formalin-induced nociceptive responses.

Several factors have been proposed to account for the differences observed between men and women in pain perception. One of these is female and male gonadal hormones. In order to verify this assumption, a hormone replacement (pellets inserted subcutaneously) of (1) 17beta-estradiol, (2) progesterone, (3) 17beta-estradiol + progesterone or (4) testosterone have been performed in gonadectomized female and male Sprague-Dawley rats. Twenty-one days after the hormonal replacement, a formalin test was performed. The nociceptive responses were divided in three distinct phases: acute (phase I), inhibitory (interphase) and tonic (phase II). After analysis, we observed that testosterone has a hypoalgesic effect on phases I and II of the formalin test. At the opposite, female hormones act only on the interphase: the combination of 17beta-estradiol and progesterone in gonadectomized rats reestablishes the weaker nociceptive pain reduction during the interphase as it is observed in the intact female. These effects were not gender specific since they had the same action in female and male. Our results permit to believe that testosterone plays a protective role in pain perception. Moreover, the female hormones act mainly on pain inhibition mechanisms (interphase), suggesting that the prevalence of certain chronic pain conditions in women could be related to a deficit of these pain inhibitory mechanisms rather than an increased nociceptive activity.

Analysis of Variance↗

PubMed2001

Therapeutic potential of PKC inhibitors in painful diabetic neuropathy.

Diabetic neuropathy accompanied by anomalies in pain perception is one of the most frequent complications in insulin-dependent diabetes in humans. Many clinical and experimental studies have suggested that diabetes or hyperglycaemia alters pain sensitivity. In humans, diabetic neuropathy can be associated with burning, tactile hypersensitivity. Behavioural reactions of hyperalgesia in animal models of diabetes have been described. However, the aetiology of these disturbances is still unknown, although metabolic factors such as hyperglycaemia or neurotransmitter alteration may be involved. Activation of protein kinase C (PKC) has been implicated in changes in pain perception. Phorbol esters, which activate PKC, enhance the thermal hyperalgesia in diabetic mice and enhance nociceptive responses after tissue injury induced by formalin. Electrophysiological experiments have shown that activation of PKC leads to long-lasting enhancement of excitatory amino acid-mediated currents in dorsal horn neurones and trigeminal neurones. Thus, activation of PKC may underlie the neuronal sensitisation that produces hyperalgesia in diabetic neuropathy.

Animals↗

PubMed2001

Fish, amphibian, and reptile analgesia.

Pain perception and appropriate behavioral responses are important for survival. The conservation of the opioid ligand and receptor suggests evolution of opioid receptors mediating antinociception throughout vertebrate phylogeny. Fish, amphibians, and reptiles have appropriate neurologic components, display the appropriate behavior in response to a painful stimulus, and possess antinociceptive mechanisms to modulate pain. Because pain perception in these species is therefore likely to be analogous to that of mammals, invasive and painful procedures should always be accompanied by appropriate analgesia and anesthesia. Although specific doses have not been established in clinical trials, clinicians should attempt to provide lower vertebrates with appropriate analgesia during painful procedures. Further experimental and clinical investigations are necessary to expand the current veterinary literature in the area of pain and analgesia in lower vertebrates such as fish, amphibians, and reptiles.

Amphibians↗