En studie til som viser at smertestillende krem påført på huden kan dempe trykksensitivitet i triggerpunkter.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337242/

3 forskjellige kremer ble brukt: the Ben-Gay Ultra Strength Muscle Pain Ointment (BG), the Professional Therapy MuscleCare Roll-on (PTMC roll-on) and Motion Medicine Cream (MM)

With regards to pressure threshold, PTMC roll-on, BG and MM showed significant increases in pain threshold tolerance after a short-term application on a trigger points located in the trapezius muscle. PTMC roll-on and BG were both shown to be superior vs placebo while PTMC was also shown to be superior to IH in patients with trigger points located in the trapezius muscle on a single application.

Several studies have investigated the effect of such topicals in the treatment of osteoarthritis, particularly of the knee [18,19]. However, there appears to be a lack of studies investigating the effects of topical agents for the treatment of MPS or MTrP. A randomized, placebo-blinded clinical trial of non-pharmacological topical analgesics was conducted comparing leading national and professional brands in the treatment of a myofascial trigger point.

The effectiveness of the topical analgesics that showed clinically significant improvements in cervical spine pressure threshold may be due to several factors. Eucalyptus oil, that was found in the PTMC solution, has been shown to transport active ingredients deep into the subcutaneous tissues [28,29]. Camphor and menthol, found in both BG and PTMC, have been proven to provide immediate pain relief [19,30,31]. Glucosamine sulfate, chondroitin sulfate, dimethyl sulfoxide and Boswellia serrata extract, found in the PTMC roll-on formulation, have been shown to improve circulation and reduce inflammation, thus reducing pain in the short-term [19,32,33]. In addition, magnesium chloride, which is unique to the PTMC roll-on, has been shown to be effectively absorbed through the dermis into muscle [34,35].

This study demonstrated that some topical analgesic products do reduce myofascial pain or tenderness.

PTMC roll-on and BG were significantly superior to the placebo in the short-term reduction of myofascial tenderness. Furthermore, the PTMC roll-on demonstrated that it was significantly superior to the IH in the short-term reduction of myofascial tenderness.

En studie som gjennomgår smertestillende behandling av huden. Nevner at den smertedempende effekten, både for akutt og kronisk smerte, er like god som piller, men uten systemiske bivirkninger.

http://www.ncbi.nlm.nih.gov/pubmed/23374622

Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects.

Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy.

Komplett gjennomgang av alle mulige mekanismer bak smerte, spesielt relatert til senesmerter.

Nevner noe svært spennende og at senesmerter, feks i achilles, kan være mer pga beskyttelse enn pga betennelse eller nocicepsjon. Derfor blir det vondt ved mer bevegelse. Hjernen prøver å beskytte kroppen mot for hard bevegelse, men feilberegner intensiteten og skaper smerte før det er nødvendig.

http://www.ncbi.nlm.nih.gov/pubmed/24027089

Finnes i sin helhet på BodyInMind sin hjemmeside.

Clinicians and researchers distinguish between physiolog- ical and pathophysiological pain. Physiological or ‘noci- ceptive’ pain is considered to reflect activation of primary nociceptors following actual or impending tissue damage or in association with inflammation. This type of pain is a helpful warning sign and is considered to be of evolu- tionary importance. Pathophysiological pain is associated with functional changes within the nervous system, such as ectopic generation of action potentials, facilitation of syn- aptic transmission, loss of synaptic connectivity, formation of new synaptic circuits, and neuroimmune interactions as well as cortical topographical changes [17], making it resistant to tissue-based treatments and it appears to pro- vide no evolutionary advantage or helpful warning.

Modern under- standing of pain suggests that nociception is neither suffi- cient nor necessary for pain [27]. Nociception refers to activity in primary afferent nociceptors—unmyelinated C fibres and thinly myelinated Ad fibres—and their projec- tions to the cortex via the lateral spinothalamic tract (Fig. 1). The projections terminate in multiple regions but predominantly the thalamus, which transmits impulses to the somatosensory cortex.

Pain, on the other hand, is an emergent property of the brain of the person in pain [28]. A useful conceptualisation is that pain emerges into consciousness in association with an individually specific pattern of activity across cortical and subcortical brain cells [29].

The relationship between nociception and pain becomes more tenuous as pain persists, and research has uncovered profound changes in the response profile of neurons within the nociceptive neuraxis.

Allodynia and primary hyperalgesia are attributed to sen- sitisation of the primary nociceptor and relate to the area of usual pain. In tendinopathy, if normally pain-free move- ments, for example jumping, evoke tendon pain, this can be termed allodynia. If palpation of the Achilles tendon evokes more pain than usual, this can be termed primary hyperalgesia.

Secondary hyperalgesia and allodynia are attributed to sensitisation of nociceptive neurons within the central nervous system (CNS), collectively called central sensiti- sation, and relate clinically to areas away from the primary ‘zone’. Tenderness and evoked pain that spread, in a non- dermatomal, non-peripheral nerve distribution is best explained by central sensitisation [36].

Glial cells, not yet investigated in tendon but evident in other connective tissues [51], share a bone marrow lineage [52] and an immune role. Glial cells, which are capable of neurotransmission in chronic injury [53], communicate information between the peripheral nervous system (PNS) and CNS [54, 55] and when activated are implicated in ongoing pain [56] and may be another cell type potentially involved in tendon pain.

Autonomic nerves, particularly sympathetic nerve endings in blood vessel walls [65], have been reported in the tendon, peritendon and endotendon of the patellar tendon [66, 67]. Sensory and sympathetic perivascular innervation of the walls of large and small blood vessels occur in peritendinous loose connective tis- sue, and there are some sensory nerve endings in the superficial endotendon [61].

Neuropeptides such as SP and calcitonin gene-related peptide (CGRP) transmit signals across a synapse. Both SP and CGRP are released by the terminals of nociceptors and SP has been shown to be released by tenocytes. SP afferent immunoreactivity has been demonstrated at the enthesis [106] and in tendon tissue [61, 64], which indicates thin fibre sensory innervation, most likely serving a nociceptive function. SP [and its receptor, neurokinin-1 receptor (NK-1 R)] and CGRP have also been identified in nerve fascicles in large and small blood vessels in tendinopathy [107]. Binding of SP to its receptor has been associated with the transmission of nociception [108].

SP can cause vasodilation and protein extravasation in surrounding tissue—a process termed neurogenic or pep- tidergic inflammation. SP increases cell metabolism, cell viability and cell proliferation in tenocytes [109]. The peptidergic inflammatory mechanism of nociceptors is initiated by nociceptor activation. However, antidromic mechanisms driven within the CNS can lead to peptidergic inflammation and this raises the possibility that central mechanisms influence tendon pain.

All cells and tissues require the maintenance of intracel- lular and tissue pH, as many processes and proteins only function within specific pH ranges [44]. Cell membrane potential, which is the difference in voltage between the inside and outside of the cell, determines the excitability of the cell and is influenced by tissue pH. Lactate can decrease pH, and microdialysis of tendinopathic tissue showed lactate levels at rest were double that shown in healthy control tendon [121]. Increased lactate, due to a predominant anaerobic metabolism, occurs in tendons of older people as well as tendinopathy [122, 123], and is compounded by the high metabolic rate in tendon pathol- ogy (25 times that of normal tendon) [124].

At physiological pH, lactic acid almost completely dis- sociates to lactate and hydrogen ions; the latter are known to modulate nociceptor activity and alter ion channel expression.

Lactate can stimulate collagen production and deposition, activate tenocytes [125] and increase vascular endothelial growth factor (VEGF) and neovascularisation [126]. Lactate also closes the inhibitory gap junctions between rows of tenocytes, which may exaggerate response to loading [127].

Accumulated lactate has been associated with pain in other tissues such as cardiac and skeletal muscle and the intervertebral disc (IVD), but it has not been fully inves- tigated for tendons. It is notable that tendon pain has some features that are consistent with accumulated lactate: rapid easing in symptoms after a change of posture (sustained positions are painful in tendinopathy), poor response to anti-inflammatory medication (true in tendons for most anti-inflammatory medications, those that alter pain and function appear to do so by tenocyte down-regulation and PG inhibition [128, 129] and sometimes no evidence of clear pathology [76].

Ion channels, present in cell membranes, alter the flow of ions in and out of a cell and respond to voltage, movement or chemicals. Ion channels in tenocytes may perform a number of roles, including mediation of calcium signalling, osmoregulation and cell volume control, control of resting membrane potential levels and the detection of mechanical stimuli [130]. Ion channels are important in tendon pain; they may be involved in sensing the nociceptive stimuli, communicating with the afferent nerves and neuronal transmission to and within the cortex.

Ion channel expression is likely to change in tendinopathy because of a more acidic environment due to excess lactate. A decrease of the extracellular pH influences the expression of acid- sensing ion channels (ASICs) [131]. The magnitude of currents in ASICs is sufficient to initiate action potentials in neurons [131]; ASICs are activated quickly by hydrogen ions and inactivate rapidly despite continued presence of low pH, exhibiting features of saturation.

ASICs have been associated with painful conditions that have accompanying tissue acidosis and ischaemia, and they were therefore originally thought to only be expressed by neurons.

Ion channel expression in tenocytes may change, but ion channel expression in the afferent nerve may also change in response to repeated activation [36]. This sensitises the primary neuron to the very stimulus that evoked the adjustment.

Ion channels are normally closed in the absence of a stimulus, but open for a few milliseconds to allow equal- isation along an electrical gradient [153]. With prolonged (chemical or electrical) stimulation, many of these chan- nels close and desensitise, leaving them refractory to fur- ther opening unless the stimulus is removed.

Although ASICs have not been studied in normal, pathological or painful tendons, the tendon environment can become acidic [121] to levels that would open ASIC channels if they were expressed by tenocytes or neurons.

Desensitisation occurs with persistent stimulation of ASICs after approximately 3 min [154], which may explain the clinical feature of tendons being initially painful during activity then warming up. Recovery from desensitisation occurs slowly, over many hours, which may fit with later pain and stiffness. ASICs are rapidly activating and inac- tivating (\5 ms to activate, 400 ms to deactivate) [155] which may also fit with the on/off nature of tendon pain. Further investigation of the presence and role of ion channels in tendon pain is warranted.

There may be non-nociceptive mechanisms that play a noci- ceptive role in tendon pain. One such mechanism may be related to an internal calculation of tendon load. This idea is consistent with the modern idea of pain being about protection and not dependent on nociception, and shares characteristics with the central governor theory of fatigue [188].

Solid gjennomgang av mechanoreceptorer i forskjellige deler av kroppen, muskler, ledd og hud.

Nevner bl.a. at ruffini er viktige mechanoreceptorer i ligamenter og ledd.

Og at muskelspindler er er svært sensitive og kan reagere på trykk og vibrasjon også. Men sammen med ruffinier, så oppfatter ikke hjernen enkeltvis spindel-stimulans. De må være flere for at hjernen skal reagerer.

Nevner også en tredje type mechanoreceptoer, SAIII, som reagerer på hudstrekk. Dette må undersøkes videre.

http://www.ncbi.nlm.nih.gov/pubmed/15730450

From this work, we know that there is specificity in the sensory channels: electrical stimulation of a single Meissner or Pacinian corpuscle generates frequency dependent illusions of ‘flutter’ or ‘vibration’, whereas microstimulation of a single Merkel afferent can produce a percept of ‘pressure’ and stimulation of a single joint afferent can evoke a sensation of ‘joint rotation’. Interestingly, the input from a single Ruffini ending in the skin cannot be perceived and the same is true of muscle spindle afferents.

Meissner and Merkel endings have very small receptive fields and respond only to local forces. Pacinian corpuscles have an exquisite sensitivity to brisk mechanical events and could respond to such stimuli transmitted through the bone to a remote receptor, but would not be able to encode sustained forces. Ruffini endings also respond to forces applied remote to the receptive field and, unlike the Pacinian corpuscles, respond in a sustained fashion, but would their signals be perceived? Like muscle spindles, it is possible that the coactivation of many Ruffini endings could provide meaningful information.

The present paper will deal only with what is known about the properties of mechanosensitive endings in skin, joint and muscle in human subjects.

MECHANORECEPTORS IN JOINTS AND LIGAMENTS

Because they are located at the interfaces between bones, mechano- receptors within the joint capsule and ligaments could, conceivably, respond to forces transmitted through the bone. Mechanoreceptors in the posterior capsule of the cat knee joint, identified as Ruffini endings, maintain a sustained discharge to a constant stimulus.

Ruffini and Golgi-like receptors have also been identified in the human knee joint, as have Pacinian corpuscles.35 Microelectrode record- ings from the median and ulnar nerves of awake human subjects have shown that mechanoreceptors associated with the inter- phalangeal joints and metacarpophalangeal joints, also believed to be Ruffini endings, do not respond to forces applied to bone when there is no movement of the joint and have very high mechanical thresholds to indentation applied over the joint capsule.11,12 Although they do respond to joint movements, they respond primarily at the limits of angular excursion.

MECHANORECEPTORS IN TENDONS

Tendons contain specialized sensory endings, the encapsulated Golgi tendon organs, the long axes of which are orientated in series with the collagenous fibres of the tendon and the muscle fibres to which they are attached. Because of this in-series coupling to muscle fibres, Golgi tendon organs are ideally suited to encode the forces developed by the contracting muscle fibres. However, Golgi tendon organs are notoriously poor at encoding changes in muscle length.36,37 As such, these endings do not respond to the longi- tudinal strains associated with passive joint rotation, but can respond to punctate compressive forces applied directly to the receptive field within the musculotendinous junction or tendon proper.

MECHANORECEPTORS IN MUSCLES

Muscles contain highly specialized stretch receptors, the muscle spindles, that have been the subject of much investigation. Each muscle spindle comprises several intrafusal (‘within the spindle’) muscle fibres enclosed within a capsule. There are two types of sensory ending, the primary ending and the secondary ending, both of which adapt slowly to a maintained stretch.

Unlike the Golgi tendon organs, muscle spindles are arranged in parallel to the muscle fibres, rendering them incapable of encoding forces generated by the contracting muscle, but very sensitive to length changes within the muscle.

ving an efferent innervation: activation of fusimotor (gamma) neurons causes contraction of the intrafusal (but not extrafusal) muscle fibres, thereby recruituing a silent spindle ending, increasing its resting discarge or changing its sensitivity to imposed stretch.

These receptors can be exquisitely sensitive, respond- ing to rather light tapping, vibration or pressure applied to the skin overlying the receptive field within the muscle belly, and respond to brisk mechanical events transmitted through the tendon, as well as to sustained forces applied to the tendon. Muscle spindles are very sensitive to vibration of the muscle belly or tendon, responding to a wide range of frequencies:42 the spindle illustrated in Fig. 3 even responded to vibration over the nail of the big toe!

Muscle spindles are the sensory endings primarily responsible for our proprioceptive acuity: small-amplitude vibration applied to muscles or tendons was the first convincing demonstration that these intramuscular stretch receptors contribute to propriocep- tion.43

However, microstimulation of a single muscle spindle afferent is not perceived by the subject; apparently, the synaptic strength between spindle afferents and higher-order neurons is so weak that coactivation of many spindle afferents is required to generate perceptual responses.12

MECHANORECEPTORS IN THE SKIN

The skin contains many specialized mechanosensitive endings that subserve the broad sense of ‘touch’ and also contribute to proprioception and motor control. The majority of human micro- neurography studies have characterized the physiology of tactile afferents in the glabrous skin of the hand, but mechanoreceptors in the hairy skin of the hand, forearm, leg and face have also been examined. Microelectrode recordings from the median and ulnar nerves in human subjects have revealed the existence of four classes of low-threshold mechanosensitive afferent supplying the glabrous skin of the hand, which correspond to the four types of specialized sensory endings identified histologically:46 Meissner and Pacinian corpuscles, Merkel cell–neurite complexes and Ruffini endings.

Two classes of afferent adapt rapidly to a sustained indentation of the skin (‘fast- adapting’), types FAI and FAII, and two classes of afferent maintain their firing throughout the stimulus (‘slowly adapting’), SAI and SAII. Based on behavioural similarities with afferents recorded in the cat and monkey,47 it is believed that the FAI and FAII afferents supply the Meissner and Pacinian corpuscles, respectively, and the SAI and SAII afferents supply the Merkel cell–neurite complex and Ruffini ending, respectively.48 Type I tactile afferents have small circular or ovoid receptive fields with distinct borders, each receptive field encompassing several small zones of maximal sensitivity (‘hot-spots’) that represent the individual Meissner corpuscles supplied by a single FAI afferent and the Merkel cell–neurite complexes innervated by each SAI axon.48,49 The type II afferents have a single zone of high sensitivity and large, poorly defined borders.

Fast-adapting type I (Meissner) afferents can only be activated by discrete stimuli in a small, well-defined area. They are particularly sensitive to light stroking across the skin, responding to local shear forces and incipient or overt slips within the receptive field.

The FAII (Pacinian) afferents are exquisitively sensitive to brisk mechanical transients. Unlike the FAI afferents, FAII afferents respond vigorously to blowing over the receptive field, responding to the fricative quality of the airflow generated by the experimenter blowing through pursed lips onto the receptive field area (they do not respond when blowing through a straw, for example). This is illustrated in Fig. 4.

Slowly adapting type I afferents (Merkel) characteristically have a high dynamic sensitivity to indentation stimuli applied to a discrete area and often respond with an off-discharge during release. Although the SAII afferents do respond to forces applied normal to the skin, a unique feature of the SAII afferents is their capacity to respond also to lateral skin stretch.

Five classes of myelinated tactile afferent have been recorded from the lateral antebrachial cutaneous nerve, which supplies the hairy skin of the human forearm: two types of slowly adapting afferent (SAI and SAII) that can be classified in a similar fashion to those in the glabrous skin and three types of rapidly adapting afferent (hair units, field units and Pacinian units).51

Hair units respond specifically to movements of individual hairs and air puffs onto the receptive field, whereas field units respond to actual skin contact. Hair units in the forearm have large ovoid or irregular receptive fields composed of multiple sensitive spots that corresponded to individual hairs. On average, each afferent supplies 20 hairs.51 The field units show a similar arrangement of multiple high-sensitivity spots11–13 making up a similarly large area, although the individual spots are larger and less isolated than those of the hair units.

Unlike glabrous skin, the hairy skin is only loosely connected to the subcutaneous tissues, thereby allowing greater stretch and, hence, greater activation of stretch-sensitive cutaneous afferents.53–55 There do appear to be significant differences in the movement sensitivity of tactile afferents in the non-glabrous and glabrous skin. For instance, 92% of the afferents on the dorsum of the hand responded to finger movements,53 whereas only 68% of afferents on the palmar side of the hand responded to passive finger movements11 and 77% responded to active movements.56

The FAI afferents respond only to movements of the joint over which they are located, but both the SAI as well as SAII afferents are very sensitive to the skin stretch associated with finger movements, whether this is produced by rotation of the nearest joint or by movements of remote digital joints. The static sensitivity to stretch is high for both classes of slowly adapting afferent:54 when measured at an equivalent joint angle, the static sensitivity of the SAI and SAII afferents is similar to that of muscle spindle endings in the long extensors of the fingers, 0.2–0.5 Hz per degree of rotation of the metacarpophalangeal joint.37,54 Figure 5 shows the behaviour of an SAI afferent recorded from the common peroneal nerve, cutaneous fascicles of which innervate the hairy skin on the dorsum of the foot and the lateral aspect of the leg.

It responded in a slowly adapting fashion to punctate stimuli applied within its receptive field, but also responded to skin stretch applied remote to the receptive field. Indeed, this receptor responded to skin stretch applied 5 cm proximal to the ankle, some 25 cm away!

Recently, Edin57 has shown that there may be a third type of slowly adapting receptor in hairy skin; the so-called SAIII was found in recordings from the lateral cutaneous femoral nerve, which supplies the anterior thigh and knee area and possesses properties intermediate between the SAI and SAII afferent types. Like these two classes, the SAIII exhibits a high static and dynamic sensitivity to skin stretch, responding with high fidelity to movements of the knee joint.

Small movements may also be sensed by specialized mechanoreceptors in the skin overlying the bone: FAII (Pacinian) and SAII (Ruffini) afferents can respond to stimuli applied remotely to their receptive field, as can SAI (Merkel) afferents in the more mobile hairy skin. The other types of cutaneous mechanoreceptor respond to stimuli applied only within their small receptive fields.