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Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hypoalgesia in the referred pain areas after bilateral injections of hypertonic saline into the trapezius muscles of men and women: a potential experimental model of gender-specific differences.

OBJECTIVE: The study was to assess the local pain intensity, referred pain patterns, and changes in the pressure pain thresholds of the local and referred pain areas following bilateral injections of hypertonic saline into trapezius muscles and to delineate gender differences in pain profile and the possible modulation of pressure pain thresholds. METHODS: Fifteen healthy men and women each participated. Pain intensity and areas were assessed after bilateral injections. The pressure pain thresholds in the trapezius and posterolateral neck muscles (referred pain areas) were measured before and 7.5 and 15 minutes postinjection. RESULTS: The time to maximal pain intensity was significantly shorter after the second injection than after the first injection. Patients exhibited a bilaterally symmetrical distribution of pain areas that included the neck to shoulder angle and the posterolateral neck. Bilateral injections significantly elevated pressure pain thresholds in the right and left posterolateral neck muscles 7.5 and 15 minutes postinjection. In men but not women, the pressure pain thresholds measured in the posterolateral neck muscles 7.5 and 15 minutes after the second injection were higher than those after the first injection and also higher than those after the second injection in women, men tolerated more pressure than women at all time points. DISCUSSION: These findings indicate that both excitatory and inhibitory mechanisms modulate pain response characteristics in bilateral neck-shoulder pain conditions and suggest that there may be a more potent inhibitory control mechanism in men than women. This experimental model may be potentially used to detect gender differences in descending inhibition.

Adult↗

Referred pain and hyperalgesia in human tendon and muscle belly tissue.

The sensitivity of tendon and tendon-bone junction is not fully described although these tissues have high clinical impacts. This study assessed (1) pain intensity and referred pain caused by hypertonic saline injection to the proximal tendon-bone junction (PTBJ), tendon and muscle belly sites of tibialis anterior muscle and (2) pressure pain sensitivity, pre, during and post hypertonic saline injections. Eighteen subjects (14 males and 4 females) participated. Subjects also had constant mechanical stimulation for 120s at 130% of baseline pressure pain threshold (PPT) during which VAS parameters were recorded. VAS parameters after hypertonic saline for PTBJ (VAS area, VAS peak), and tendon sites (VAS area, duration and time to maximum VAS) were significantly (P < 0.05) higher than muscle belly. During hypertonic saline pain all three sites displayed local and frequently enlarged and referred pain areas. Hypertonic saline pain at the PTBJ and tendon transiently increased pressure sensitivity at these sites (P < 0.05). When referred pain was caused by mechanical stimulation it occurred predominantly at the PTBJ and tendon sites (86% cases). Constant mechanical stimulation caused steadily increasing pain (summation of pain) at all sites. Hypertonic saline pain at the tendon and PTBJ caused significantly higher (P < 0.001) final VAS scores compared to the muscle belly site. The results indicate the PTBJ and tendon sites are more sensitive and susceptible to sensitisation by hypertonic saline than muscle belly. Furthermore, there may be site specific central changes reflected by the differences in the results regarding sensitivity and summation over time.

Adult↗

Referred pain in the lower leg -- a cause of delayed diagnosis.

Three patients presenting with ankle pain are described. In each case the pain was referred from a lesion in the proximal tibia (two osteoid osteomas; one stress fracture). There was considerable delay in diagnosis in two of these cases. It would appear that pain referred from the proximal lower leg to the ankle is not well recognized as a clinical entity. In such cases, radiography of the more proximal limb is suggested. If this proves negative, a bone scan may then be performed.

Adolescent↗

Referred pain from trapezius muscle trigger points shares similar characteristics with chronic tension type headache.

Referred pain and pain characteristics evoked from the upper trapezius muscle was investigated in 20 patients with chronic tension-type headache (CTTH) and 20 age- and gender-matched controls. A headache diary was kept for 4 weeks in order to confirm the diagnosis and record the pain history. Both upper trapezius muscles were examined for the presence of myofascial trigger points (TrPs) in a blinded fashion. The local and referred pain intensities, referred pain pattern, and pressure pain threshold (PPT) were recorded. The results show that referred pain was evoked in 85% and 50% on the dominant and non-dominant sides in CTTH patients, much higher than 55% and 25% in controls (P<0.01). Referred pain spread to the posterior-lateral aspect of the neck ipsi-lateral to the stimulated muscle in both patients and controls, with additional referral to the temple in most patients, but none in controls. Nearly half of the CTTH patients (45%) recognized the referred pain as their usual headache sensation, i.e. active TrPs. CTTH patients with active TrPs in the right upper trapezius muscle showed greater headache intensity and frequency, and longer headache duration than those with latent TrPs. CTTH patients with bilateral TrPs reported significantly decreased PPT than those with unilateral TrP (P<0.01). Our results showed that manual exploration of TrPs in the upper trapezius muscle elicited referred pain patterns in both CTTH patients and healthy subjects. In CTTH patients, the evoked referred pain and its sensory characteristics shared similar patterns as their habitual headache pain, consistent with active TrPs. Our results suggest that spatial summation of perceived pain and mechanical pain sensitivity exists in CTTH patients.

Adult↗

Perceptual integration of intramuscular electrical stimulation in the focal and the referred pain area in healthy humans.

The aim of the study was to investigate the perceptual integration of simultaneous stimulation in a focal and a referred pain area to investigate whether referred pain is mainly caused by facilitation of on-going input from the referred pain area by stimulation in the focal pain area or if referred pain is a consequence of misinterpretation of the origin of inputs from the focal pain area. Pain was induced in twelve healthy individuals by intramuscular electrical stimulation in the left infraspinatus muscle (MI) or the left dorsolateral upper arm (UA), i.e. the area of referral commonly reported from stimulation in MI. Conditioning stimulation consisted of, in a counterbalanced order, no stimulation (baseline) and pain intensity rated as 2/10 and 4/10, respectively, on a category scale. During conditioning stimulation in MI, sensitivity to test stimuli was assessed in UA and vice versa. The test stimuli consisted of i.m. electrical stimulation corresponding to the perception threshold to innocuous electrical stimulation, the electrical pain threshold (EPT), and pain intensity rated as 2/10, 4/10 and 6/10, respectively. Conditioning stimulation corresponding to 2/10 did not result in a statistically significant change in sensitivity to any test stimuli in either location. During conditioning stimulation corresponding to 4/10 in m. infraspinatus, all twelve subjects reported referred pain in the dorsolateral upper arm. Compared to baseline, EPTs decreased in the referred pain area (P<0.001), while no other statistically significant changes in sensitivity to test stimuli were seen. Conditioning stimulation corresponding to 4/10 in the dorsolateral upper arm gave rise to referred pain in one individual (area of m. biceps brachii), and no statistically significant changes were seen in the sensitivity to electrical stimuli in m. infraspinatus. In conclusion, an effect at pain threshold level only was documented during simultaneous stimulation in the focal and referred pain area, which does not support facilitation of inputs from the referred pain area as the main mechanism generating referred pain. Instead, referred pain is most likely a consequence of misinterpretation of the origin of input from the stimulated focal pain area, due to excitation of neurones somewhere along the neuroaxis with projected fields in the referred pain area. The fact that conditioning stimulation in m. infraspinatus generated referred pain in the dorsolateral upper arm, but not vice versa suggests that the divergence of the input is not reciprocally arranged.

Adult↗

Primary soft tissue tumours of the pelvis causing referred pain in the leg.

Referred pain in the leg is occasionally due to a pelvic soft tissue tumour. Among 11 patients who presented this way, one had a lymphoma, one had a benign schwannoma, and nine had soft tissue sarcomas. Most patients had undergone a variety of procedures, including laminectomy, before the correct diagnosis was established. In five cases, an accurate diagnosis was obtained by needle biopsy. The lymphoma responded to chemotherapy, and the benign schwannoma was excised. Of the nine patients with soft tissue sarcoma, six underwent marginal/intracapsular excision, three receiving supplementary radiotherapy, and two were treated by nonsurgical means. Hindquarter amputation was technically impossible or inappropriate in these cases. All those with high-grade tumours have died or have metastases. Of four patients with low-grade tumours, three have exhibited only slow disease progression. Careful judgment and a precise histopathological diagnosis are required in planning treatment for patients with pelvic soft tissue tumours causing referred pain in the leg.

Adult↗

Pain in the ear--with special reference to referred pain.

This study was carried out to determine the true pathology in a group of patients (100) who presented to the outpatient clinic with pain in the ear, as their main or only complaint. An analysis of the results is presented and the literature is reviewed. From this study, it appears that referred pain is commoner than pain due to lesions in the ear itself, as seen in an Out-Patient Clinic.

Adolescent↗

Influence of biased clinician statements on patient report of referred pain.

AIMS: The purpose of this study was to examine the influence of clinician bias on patients' reports of referred pain. Diagnosis of temporomandibular disorders is dependent on subjective reports of pain and referred pain upon manual muscle palpation. The influence of biased clinician statements in such subjective reports has not been previously investigated. METHODS: Forty subjects with pain and who met specific inclusion criteria were randomly assigned to 1 of 2 experimental groups. One group was subjected to a standardized biasing statement, while the other group was not. Tender points in the masseter muscle were then stimulated with a pressure algometer to the pressure-pain threshold. Subjects then recorded the presence or absence, location, intensity, and unpleasantness of any referred pain. State-trait anxiety and social desirability were also assessed to explore the possibility that anxiety levels or subjects' desires to please the experimenter influenced results. RESULTS: The biased group reported increased presence (P < 0.01), intensity (P < 0.001), and unpleasantness (P < 0.003) of referred pain as compared to the non-biased group. There were no differences between groups on state-trait anxiety or social desirability (P > 0.05). CONCLUSION: These data suggest that patient reports of pain referral may be subject to clinician bias, and recommendations to control this bias are offered.

Adolescent↗

Injection of hypertonic saline into musculus infraspinatus resulted in referred pain and sensory disturbances in the ipsilateral upper arm.

A confounding factor in the analysis of chronic pain patients is the finding of somatosensory disturbances not only in neuropathic pain patients, but also in a subgroup of patients with musculoskeletal pain. The purpose of the study was to examine if referred pain, induced by intramuscular injections of hypertonic saline (5% NaCl) into the left musculus infraspinatus, resulted in somatosensory alterations. Thermal sensitivity, pressure pain sensitivity, as well as low threshold mechanoreceptive function, were assessed in the referred pain area and the homologous contralateral site before, during and following the injections. In 10 out of 12 subjects the procedure induced only referred pain localized in the dorsolateral part of the ipsilateral proximal upper arm. In this referred pain area there was a significantly decreased sensitivity to light touch, as tested with von Frey filaments, during the pain period and the post-injection period compared to the contralateral side (p<0.004 and p<0.009, respectively). A trend for thermal hypoaesthesia, which was only demonstrable in the sum of warm and cold thresholds, was found in the referred pain area, but not contralaterally, during the pain period compared to the pre-injection period. Significantly increased sensitivity to threshold and suprathreshold heat pain was found bilaterally during post-injection assessments (p<0.02 and p<0.006, respectively). There were no statistically significant changes in sensitivity to innocuous thermal stimuli when assessing the two percepts separately, or to pressure pain or brush-evoked touch. In conclusion, intramuscular injections of hypertonic saline resulted in referred pain and tactile hypoaesthesia in the referred pain area.

Adult↗

Somatosensory changes in the referred pain area in patients with acute cholecystitis before and after treatment with laparoscopic or open cholecystectomy.

BACKGROUND: Visceral pain can lead to hypersensitivity in the referred pain area. In patients with chronic visceral pain this somatic hypersensitivity can persist for years. As 25%-40% of patients continue to have symptoms after cholecystectomy, whereof no explanation for pain can be offered in up to 30%, it could be hypothesized that altered sensory characteristics induced by acute cholecystitis could persist in some patients and thus be responsible for postcholecystectomy pain. The aim of this study was to investigate the somatosensory sensitivity in the referred pain area in patients with acute cholecystitis before and after cholecystectomy. METHODS: Patients with acute cholecystitis were studied before (n = 30) and after (n = 18) treatment. Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical stimulation was studied in the referred pain area and in the control area on the contralateral side of the abdomen. RESULTS: Significant hypersensitivity in the referred pain area was detected in patients with acute cholecystitis. The somatic sensitivity was normalized after cholecystectomy. CONCLUSIONS: Acute cholecystitis leads to hypersensitivity in the referred pain area. Persistent hypersensitivity, as earlier reported after chronic visceral pain, was not seen aftiser cholecystectomy, indicating that this mechanism may not play a major role in patients with postcholecystectomy pain syndrome. The possible role in patients operated on for chronic gallstone pain has still to be investigated.

Abdominal Pain↗

Referred pain distribution of the cervical zygapophyseal joints and cervical dorsal rami.

The purpose of this study was to determine the distribution of referred pain from the cervical zygapophyseal joints (C0/1 to C7/Th1) and the cervical dorsal rami (C3 to C7). The subjects were 61 patients who had occipital, neck, and shoulder pain of suspected zygapophyseal origin in whom pain was reproduced by injection of contrast medium into the joints or by electrical stimulation of the dorsal rami. Under fluoroscopic control, the zygapophyseal joints from C0/1 to C7/Th1 were stimulated by the injection of contrast medium and while electrical stimulation of the cervical zygapophyseal dorsal rami at segments C3 to C7 was performed during facet denervation. If injection or electrical stimulation reproduced the patient's usual pain, the distribution of referred pain was determined and the sites of referred pain were divided into 10 areas. A total of 181 joints and 62 segments were studied. Each joint and dorsal ramus produced referred pain with a characteristic distribution. The main distribution of referred pain was as follows. Pain in the occipital region was referred from C2/3 and C3, while pain in the upper posterolateral cervical region was referred from C0/1, C1/2, and C2/3. Pain in the upper posterior cervical region was referred from C2/3, C3/4, and C3, that in the middle posterior cervical region from C3/4, C4/5, and C4, and that in the lower posterior cervical region from C4/5, C5/6, C4, and C5. In addition, pain in the suprascapular region was referred from C4/5, C5/6, and C4, that in the superior angle of the scapula from C6/7, C6, and C7, and that in the mid-scapular region from C7/Th1 and C7.

Cervical Vertebrae↗

The effect of compression and regional anaesthetic block on referred pain intensity in humans.

The mechanisms underlying local and referred muscle pain are poorly understood. The aim of this experiment was to determine to which degree referred pain is dependent on peripheral or central mechanisms. This was studied by blocking sensory input from the referred pain area. Intramuscular electrical stimulation in the right anterior tibial muscle induced local muscle pain and referred pain in 12 subjects. Nerve blocks were applied on the lower limb between the local and the referred pain area for 60 min. Three different studies were performed: (1) no nerve block (2) compression block, and (3) compression block combined with intravenous regional anaesthesia. The referred pain intensity was assessed every 5 min. To monitor the blockade of myelinated and unmyelinated nerve fibres, touch, pinprick, position sense and heat and heat-pain detection thresholds were assessed on the dorsal side of the foot every 5 min. A significant reduction in referred pain intensity (40.5%) compared with the control experiment was found after 40 min with the compression ischemia nerve block until release of the tourniquet. In the combined nerve block experiment, a significant reduction of referred pain intensity (38.5%) was seen after 20 min and until the release of the tourniquet. There was no significant difference in the referred pain intensity between the two types of blocks. The present findings suggest that both peripheral and central mechanisms play a role in referred pain and that the myelinated fibres mediate the peripheral component.

Adult↗

Experimental muscle pain provokes long-lasting alterations of thermal sensitivity in the referred pain area.

This study explores thermal sensitivity and thermal nociception for signs of central sensitization in the area of referred muscle pain. Two groups of 24 healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years, were first trained in quantitative sensory testing and pain rating. Then, in a second session, referred pain was evoked by injection of 6% hypertonic saline into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal pain thresholds were measured within the referred pain area at a rate of 1/20 min for 60-120 min. All ss of both groups experienced referred pain mostly in the upper arm and of medium intensity. Pain lasted for approximately 12min with a shorter duration in the older group (p<0.02). The cold threshold increased significantly (p<0.001), and the warm threshold slightly, after the injection and remained high for the whole observation period (i.e. lower and higher temperatures were necessary to elicit cold and warmth, respectively). Threshold recovery was more delayed in the older age group. Of those 28 ss in whom cold pain threshold could be followed during the whole observation period, 18 ss showed an immediate threshold decrease of average 6 degrees C which outlasted the observation period. Four ss responded with a threshold increase. Heat pain thresholds were not affected in the referred pain area. Average synthetic heat threshold did not change; there were, however, distinct and lasting individual threshold shifts in either direction. Ss with lowered cold pain thresholds or evident threshold shifts for synthetic heat had also higher pain ratings. The results demonstrate that experimental muscle pain can induce long-lasting changes in thermal sensitivity and nociception. The unexpected cold threshold increase may tentatively be explained as an expression of long-term depression. The decrease of cold pain threshold or SHT in subgroups of ss may indicate central sensitization. However, the observed changes in this experiment do not provide an unambiguous indicator for central sensitization which seems to be rather individual and might depend on pain intensity and proneness to express central mechanisms of sensitization. Therefore in clinical pain states the individual pattern of sensory abnormalities has to be analysed and interpreted in addition to the pain parameters to assess central involvement.

Adult↗

Somatosensory changes in the referred pain area before and after cholecystectomy in patients with uncomplicated gallstone disease.

OBJECTIVE: It is estimated that 25-40% of patients have continuing symptoms after cholecystectomy and that 5-10% have pain. The pain may be related to central neuroplastic changes of sensory pathways induced by the gallstone disease. Such neuronal hyperexcitability can be reflected in the somatic referred pain area sharing central pathways with the gallbladder. The aim of this study was to examine somatosensory changes in the referred pain area evoked by painful gallstone attacks before and after cholecystectomy in patients with uncomplicated gallstone disease. MATERIAL AND METHODS: Thirty-seven patients with uncomplicated gallstone disease were included in the study. The sensations and pain thresholds to pinprick, pinching, pressure, thermal and electrical stimulation were studied before and 4-12 weeks after surgery in the area where the pain was referred to during the previous gallstone attacks. An area on the contralateral side of the abdomen served as the control. RESULTS: Somatosensory hyperalgesia in the referred pain area was observed in 84% of the patients before surgery. After elective cholecystectomy, none of the patients had pain complaints, and the sensibility in the referred area was normalized. CONCLUSIONS: Uncomplicated gallstone disease leads to significant hyperalgesia in the somatic referred pain area. At the time of the postoperative investigation none of the patients suffered from pain, which was reflected in the normal sensory findings in the previous referred pain area.

Adult↗